Gαq-mediated calcium dynamics and membrane tension modulate neurite plasticity.

Abstract:

:The formation and disruption of synaptic connections during development are a fundamental step in neural circuit formation. Subneuronal structures such as neurites are known to be sensitive to the level of spontaneous neuronal activity, but the specifics of how neurotransmitter-induced calcium activity regulates neurite homeostasis are not yet fully understood. In response to stimulation by neurotransmitters such as acetylcholine, calcium responses in cells are mediated by the Gαq/phospholipase Cβ (PLCβ)/phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) signaling pathway. Here, we show that prolonged Gαq stimulation results in the retraction of neurites in PC12 cells and the rupture of neuronal synapses by modulating membrane tension. To understand the underlying cause, we dissected the behavior of individual components of the Gαq/PLCβ/PI(4,5)P2 pathway during retraction and correlated these with the retraction of the membrane and cytoskeletal elements impacted by calcium signaling. We developed a mathematical model that combines biochemical signaling with membrane tension and cytoskeletal mechanics to show how signaling events are coupled to retraction velocity, membrane tension, and actin dynamics. The coupling between calcium and neurite retraction is shown to be operative in the Caenorhabditis elegans nervous system. This study uncovers a novel mechanochemical connection between Gαq/PLCβ /PI(4,5)P2 that couples calcium responses with neural plasticity.

journal_name

Mol Biol Cell

authors

Pearce KM,Bell M,Linthicum WH,Wen Q,Srinivasan J,Rangamani P,Scarlata S

doi

10.1091/mbc.E19-09-0536

subject

Has Abstract

pub_date

2020-03-19 00:00:00

pages

683-694

issue

7

eissn

1059-1524

issn

1939-4586

journal_volume

31

pub_type

杂志文章
  • Transfection of choanoflagellates illuminates their cell biology and the ancestry of animal septins.

    abstract::As the closest living relatives of animals, choanoflagellates offer unique insights into animal origins and core mechanisms underlying animal cell biology. However, unlike traditional model organisms, such as yeast, flies, and worms, choanoflagellates have been refractory to DNA delivery methods for expressing foreign...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E18-08-0514

    authors: Booth DS,Szmidt-Middleton H,King N

    更新日期:2018-12-01 00:00:00

  • A guide to simple and informative binding assays.

    abstract::The aim of binding assays is to measure interactions between two molecules, such as a protein binding another protein, a small molecule, or a nucleic acid. Hard work is required to prepare reagents, but flaws in the design of many binding experiments limit the information obtained. In particular many experiments fail ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-08-0683

    authors: Pollard TD

    更新日期:2010-12-01 00:00:00

  • Transforming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism.

    abstract::Transforming growth factor-beta1 (TGF-beta) can be tumor suppressive, but it can also enhance tumor progression by stimulating the complex process of epithelial-to-mesenchymal transdifferentiaion (EMT). The signaling pathway(s) that regulate EMT in response to TGF-beta are not well understood. We demonstrate the acqui...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.1.27

    authors: Bhowmick NA,Ghiassi M,Bakin A,Aakre M,Lundquist CA,Engel ME,Arteaga CL,Moses HL

    更新日期:2001-01-01 00:00:00

  • Rab4 regulates formation of synaptic-like microvesicles from early endosomes in PC12 cells.

    abstract::Early endosomes in PC12 cells are an important site for the formation of synaptic-like microvesicles and constitutive recycling vesicles. By immunogold electron microscopy, the small GTPase rab4 was localized to early endosomes and numerous small vesicles in the cell periphery and Golgi area of PC12 cells. Overexpress...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.11.3703

    authors: de Wit H,Lichtenstein Y,Kelly RB,Geuze HJ,Klumperman J,van der Sluijs P

    更新日期:2001-11-01 00:00:00

  • Functions of the small proteins in the TOM complex of Neurospora crasssa.

    abstract::The TOM (translocase of the outer mitochondrial membrane) complex of the outer mitochondrial membrane is required for the import of proteins into the organelle. The core TOM complex contains five proteins, including three small components Tom7, Tom6, and Tom5. We have created single and double mutants of all combinati...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-03-0187

    authors: Sherman EL,Go NE,Nargang FE

    更新日期:2005-09-01 00:00:00

  • S100A4 regulates macrophage chemotaxis.

    abstract::S100A4, a member of the S100 family of Ca(2+)-binding proteins, is directly involved in tumor metastasis. In addition to its expression in tumor cells, S100A4 is expressed in normal cells and tissues, including fibroblasts and cells of the immune system. To examine the contribution of S100A4 to normal physiology, we e...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-07-0609

    authors: Li ZH,Dulyaninova NG,House RP,Almo SC,Bresnick AR

    更新日期:2010-08-01 00:00:00

  • Microtubule motor Ncd induces sliding of microtubules in vivo.

    abstract::The mitotic spindle is a microtubule (MT)-based molecular machine that serves for equal segregation of chromosomes during cell division. The formation of the mitotic spindle requires the activity of MT motors, including members of the kinesin-14 family. Although evidence suggests that kinesins-14 act by driving the sl...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-12-1085

    authors: Oladipo A,Cowan A,Rodionov V

    更新日期:2007-09-01 00:00:00

  • Myosin vb is associated with plasma membrane recycling systems.

    abstract::Myosin Va is associated with discrete vesicle populations in a number of cell types, but little is known of the function of myosin Vb. Yeast two-hybrid screening of a rabbit parietal cell cDNA library with dominant active Rab11a (Rab11aS20V) identified myosin Vb as an interacting protein for Rab11a, a marker for plasm...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.6.1843

    authors: Lapierre LA,Kumar R,Hales CM,Navarre J,Bhartur SG,Burnette JO,Provance DW Jr,Mercer JA,Bähler M,Goldenring JR

    更新日期:2001-06-01 00:00:00

  • Wnt regulation: exploring Axin-Disheveled interactions and defining mechanisms by which the SCF E3 ubiquitin ligase is recruited to the destruction complex.

    abstract::Wnt signaling plays key roles in embryonic development and adult stem cell homeostasis and is altered in human cancer. Signaling is turned on and off by regulating stability of the effector β-catenin (β-cat). The multiprotein destruction complex binds and phosphorylates β-cat and transfers it to the SCF-TrCP E3-ubiqui...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-11-0647

    authors: Schaefer KN,Pronobis MI,Williams CE,Zhang S,Bauer L,Goldfarb D,Yan F,Major MB,Peifer M

    更新日期:2020-05-01 00:00:00

  • Molecular basis for phosphospecific recognition of histone H3 tails by Survivin paralogues at inner centromeres.

    abstract::Survivin, a subunit of the chromosome passenger complex (CPC), binds the N-terminal tail of histone H3, which is phosphorylated on T3 by Haspin kinase, and localizes the complex to the inner centromeres. We used x-ray crystallography to determine the residues of Survivin that are important in binding phosphomodified h...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-11-0904

    authors: Niedzialkowska E,Wang F,Porebski PJ,Minor W,Higgins JM,Stukenberg PT

    更新日期:2012-04-01 00:00:00

  • Abnormal intermediate filament organization alters mitochondrial motility in giant axonal neuropathy fibroblasts.

    abstract::Giant axonal neuropathy (GAN) is a rare disease caused by mutations in the GAN gene, which encodes gigaxonin, an E3 ligase adapter that targets intermediate filament (IF) proteins for degradation in numerous cell types, including neurons and fibroblasts. The cellular hallmark of GAN pathology is the formation of large...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E15-09-0627

    authors: Lowery J,Jain N,Kuczmarski ER,Mahammad S,Goldman A,Gelfand VI,Opal P,Goldman RD

    更新日期:2016-02-15 00:00:00

  • Cornichon-like protein facilitates secretion of HB-EGF and regulates proper development of cranial nerves.

    abstract::During their migration to the periphery, cranial neural crest cells (NCCs) are repulsed by an ErbB4-dependent cue(s) in the mesenchyme adjoining rhombomeres (r) 3 and 5, which are segmented hindbrain neuromeres. ErbB4 has many ligands, but which ligand functions in the above system has not yet been clearly determined....

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-08-0733

    authors: Hoshino H,Uchida T,Otsuki T,Kawamoto S,Okubo K,Takeichi M,Chisaka O

    更新日期:2007-04-01 00:00:00

  • LIMK1 regulates Golgi dynamics, traffic of Golgi-derived vesicles, and process extension in primary cultured neurons.

    abstract::In this study, we examined the subcellular distribution and functions of LIMK1 in developing neurons. Confocal microscopy, subcellular fractionation, and expression of several epitope-tagged LIMK1 constructs revealed that LIMK1 is enriched in the Golgi apparatus and growth cones, with the LIM domain required for Golgi...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-05-0328

    authors: Rosso S,Bollati F,Bisbal M,Peretti D,Sumi T,Nakamura T,Quiroga S,Ferreira A,Cáceres A

    更新日期:2004-07-01 00:00:00

  • Glycoprotein gp130 of dictyostelium discoideum influences macropinocytosis and adhesion.

    abstract::Glycoprotein gp130, found on the plasma membrane of Dictyostelium discoideum amoebae, was postulated previously to play a role in phagocytosis. The gene for gp130 was cloned and when translated, yielded a 768 amino acid preproprotein of 85.3 kDa. It had nearly 40% similarity to the 138 kDa family of glycoproteins impl...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-06-0483

    authors: Chia CP,Gomathinayagam S,Schmaltz RJ,Smoyer LK

    更新日期:2005-06-01 00:00:00

  • Identification of the nuclear localization signal in Xenopus cyclin E and analysis of its role in replication and mitosis.

    abstract::Cyclin-dependent kinase (Cdk)2/cyclin E is imported into nuclei assembled in Xenopus egg extracts by a pathway that requires importin-alpha and -beta. Here, we identify a basic nuclear localization sequence (NLS) in the N-terminus of Xenopus cyclin E. Mutation of the NLS eliminated nuclear accumulation of both cyclin ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-07-0449

    authors: Moore JD,Kornbluth S,Hunt T

    更新日期:2002-12-01 00:00:00

  • Roles of polymerization dynamics, opposed motors, and a tensile element in governing the length of Xenopus extract meiotic spindles.

    abstract::Metaphase spindles assemble to a steady state in length by mechanisms that involve microtubule dynamics and motor proteins, but they are incompletely understood. We found that Xenopus extract spindles recapitulate the length of egg meiosis II spindles, by using mechanisms intrinsic to the spindle. To probe these mecha...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-02-0174

    authors: Mitchison TJ,Maddox P,Gaetz J,Groen A,Shirasu M,Desai A,Salmon ED,Kapoor TM

    更新日期:2005-06-01 00:00:00

  • Laminin 511 partners with laminin 332 to mediate directional migration of Madin-Darby canine kidney epithelial cells.

    abstract::Sustained directional migration of epithelial cells is essential for regeneration of injured epithelia. Front-rear polarity of migrating cells is determined by local activation of a signaling network involving Cdc42 and other factors in response to spatial cues from the environment, the nature of which are obscure. We...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-08-0718

    authors: Greciano PG,Moyano JV,Buschmann MM,Tang J,Lu Y,Rudnicki J,Manninen A,Matlin KS

    更新日期:2012-01-01 00:00:00

  • Src-dependent TrkA transactivation is required for pituitary adenylate cyclase-activating polypeptide 38-mediated Rit activation and neuronal differentiation.

    abstract::Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent neuropeptide that possesses both neurotrophic and neurodevelopmental effects. Recently, the Rit GTPase was found to be activated by a novel Galpha/cAMP/exchange protein activated by cyclic AMP (Epac)-dependent signaling pathway and required for PAC...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-12-1033

    authors: Shi GX,Jin L,Andres DA

    更新日期:2010-05-01 00:00:00

  • An Amish founder mutation disrupts a PI(3)P-WHAMM-Arp2/3 complex-driven autophagosomal remodeling pathway.

    abstract::Actin nucleation factors function to organize, shape, and move membrane-bound organelles, yet they remain poorly defined in relation to disease. Galloway-Mowat syndrome (GMS) is an inherited disorder characterized by microcephaly and nephrosis resulting from mutations in the WDR73 gene. This core clinical phenotype ap...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E17-01-0022

    authors: Mathiowetz AJ,Baple E,Russo AJ,Coulter AM,Carrano E,Brown JD,Jinks RN,Crosby AH,Campellone KG

    更新日期:2017-09-15 00:00:00

  • Cell cycle-regulated trafficking of Chs2 controls actomyosin ring stability during cytokinesis.

    abstract::Cytokinesis requires the coordination of many cellular complexes, particularly those involved in the constriction and reconstruction of the plasma membrane in the cleavage furrow. We have investigated the regulation and function of vesicle transport and fusion during cytokinesis in budding yeast. By using time-lapse c...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-12-1090

    authors: VerPlank L,Li R

    更新日期:2005-05-01 00:00:00

  • Behaviors of individual microtubules and microtubule populations relative to critical concentrations: dynamic instability occurs when critical concentrations are driven apart by nucleotide hydrolysis.

    abstract::The concept of critical concentration (CC) is central to understanding the behavior of microtubules (MTs) and other cytoskeletal polymers. Traditionally, these polymers are understood to have one CC, measured in multiple ways and assumed to be the subunit concentration necessary for polymer assembly. However, this fra...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-02-0101

    authors: Jonasson EM,Mauro AJ,Li C,Labuz EC,Mahserejian SM,Scripture JP,Gregoretti IV,Alber M,Goodson HV

    更新日期:2020-03-19 00:00:00

  • Differential roles for actin polymerization and a myosin II motor in assembly of the epithelial apical junctional complex.

    abstract::Differentiation and polarization of epithelial cells depends on the formation of the apical junctional complex (AJC), which is composed of the tight junction (TJ) and the adherens junction (AJ). In this study, we investigated mechanisms of actin reorganization that drive the establishment of AJC. Using a calcium switc...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-01-0043

    authors: Ivanov AI,Hunt D,Utech M,Nusrat A,Parkos CA

    更新日期:2005-06-01 00:00:00

  • Transforming growth factor-beta complexes with thrombospondin.

    abstract::Thrombospondin (TSP) was demonstrated to inhibit the growth of bovine aortic endothelial cells, an activity that was not neutralized by antibodies to TSP or by other agents that block TSP-cell interactions but that partially was reversed by a neutralizing antibody to transforming growth factor-beta (TGF-beta). Similar...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.3.2.181

    authors: Murphy-Ullrich JE,Schultz-Cherry S,Höök M

    更新日期:1992-02-01 00:00:00

  • Ionizing radiation-dependent gamma-H2AX focus formation requires ataxia telangiectasia mutated and ataxia telangiectasia mutated and Rad3-related.

    abstract::The histone variant H2AX is rapidly phosphorylated at the sites of DNA double-strand breaks (DSBs). This phosphorylated H2AX (gamma-H2AX) is involved in the retention of repair and signaling factor complexes at sites of DNA damage. The dependency of this phosphorylation on the various PI3K-related protein kinases (in ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-10-0890

    authors: Friesner JD,Liu B,Culligan K,Britt AB

    更新日期:2005-05-01 00:00:00

  • Protein kinase Czeta mediates insulin-induced glucose transport through actin remodeling in L6 muscle cells.

    abstract::Protein kinase C (PKC) zeta has been implicated in insulin-induced glucose uptake in skeletal muscle cell, although the underlying mechanism remains unknown. In this study, we investigated the effect of PKCzeta on actin remodeling and glucose transport in differentiated rat L6 muscle cells expressing myc-tagged glucos...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-10-0969

    authors: Liu LZ,Zhao HL,Zuo J,Ho SK,Chan JC,Meng Y,Fang FD,Tong PC

    更新日期:2006-05-01 00:00:00

  • Three-dimensional niche stiffness synergizes with Wnt7a to modulate the extent of satellite cell symmetric self-renewal divisions.

    abstract::Satellite cells (SCs), the resident adult stem cells of skeletal muscle, are required for tissue repair throughout life. While many signaling pathways are known to control SC self-renewal, less is known about the mechanisms underlying the spatiotemporal control of self-renewal during skeletal muscle repair. Here, we m...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E20-01-0078

    authors: Moyle LA,Cheng RY,Liu H,Davoudi S,Ferreira SA,Nissar AA,Sun Y,Gentleman E,Simmons CA,Gilbert PM

    更新日期:2020-07-21 00:00:00

  • Direct and indirect roles of cyclin-dependent kinase 5 as an upstream regulator in the c-Jun NH2-terminal kinase cascade: relevance to neurotoxic insults in Alzheimer's disease.

    abstract::Significant increase in JNK, c-Jun, and Cdk5 activities are reported in Alzheimer's disease (AD). Inhibition of c-Jun prevents neuronal cell death in in vivo AD models, highlighting it as a major JNK effector. Both JNK and Cdk5 promote neurodegeneration upon deregulation; however, Cdk5 has not been mechanistically lin...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-05-0433

    authors: Sun KH,Lee HG,Smith MA,Shah K

    更新日期:2009-11-01 00:00:00

  • Dynein-dependent motility of microtubules and nucleation sites supports polarization of the tubulin array in the fungus Ustilago maydis.

    abstract::Microtubules (MTs) are often organized by a nucleus-associated MT organizing center (MTOC). In addition, in neurons and epithelial cells, motor-based transport of assembled MTs determines the polarity of the MT array. Here, we show that MT motility participates in MT organization in the fungus Ustilago maydis. In budd...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-12-1118

    authors: Fink G,Steinberg G

    更新日期:2006-07-01 00:00:00

  • The cell biology of aging.

    abstract::One of the original hypotheses of organismal longevity posits that aging is the natural result of entropy on the cells, tissues, and organs of the animal--a slow, inexorable slide into nonfunctionality caused by stochastic degradation of its parts. We now have evidence that aging is instead at least in part geneticall...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章,评审

    doi:10.1091/mbc.E14-06-1084

    authors: DiLoreto R,Murphy CT

    更新日期:2015-12-15 00:00:00

  • The proteomics of quiescent and nonquiescent cell differentiation in yeast stationary-phase cultures.

    abstract::As yeast cultures enter stationary phase in rich, glucose-based medium, differentiation of two major subpopulations of cells, termed quiescent and nonquiescent, is observed. Differences in mRNA abundance between exponentially growing and stationary-phase cultures and quiescent and nonquiescent cells are known, but lit...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-06-0499

    authors: Davidson GS,Joe RM,Roy S,Meirelles O,Allen CP,Wilson MR,Tapia PH,Manzanilla EE,Dodson AE,Chakraborty S,Carter M,Young S,Edwards B,Sklar L,Werner-Washburne M

    更新日期:2011-04-01 00:00:00