Dynamin 2 potentiates invasive migration of pancreatic tumor cells through stabilization of the Rac1 GEF Vav1.

Abstract:

:The large GTPase Dynamin 2 (Dyn2) is markedly upregulated in pancreatic cancer, is a potent activator of metastatic migration, and is required for Rac1-mediated formation of lamellipodia. Here we demonstrate an unexpected mechanism of Dyn2 action in these contexts via direct binding to the Rac1 guanine nucleotide exchange factor (GEF) Vav1. Surprisingly, disruption of the Dyn2-Vav1 interaction targets Vav1 to the lysosome for degradation via an interaction with the cytoplasmic chaperone Hsc70, resulting in a dramatic reduction of Vav1 protein stability. Importantly, a specific mutation in Vav1 near its Dyn2-binding C-terminal Src homology 3 (SH3) domain prevents Hsc70 binding, resulting in a stabilization of Vav1 levels. Dyn2 binding regulates the interaction of Vav1 with Hsc70 to control the stability and subsequent activity of this oncogenic GEF. These findings elucidate how Dyn2 activates Rac1, lamellipod protrusion, and invasive cellular migration and provide insight into how this specific Vav is ectopically expressed in pancreatic tumors.

journal_name

Dev Cell

journal_title

Developmental cell

authors

Razidlo GL,Wang Y,Chen J,Krueger EW,Billadeau DD,McNiven MA

doi

10.1016/j.devcel.2013.02.010

subject

Has Abstract

pub_date

2013-03-25 00:00:00

pages

573-85

issue

6

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(13)00122-6

journal_volume

24

pub_type

杂志文章
  • Morpholinos Do Not Elicit an Innate Immune Response during Early Xenopus Embryogenesis.

    abstract::It has recently been reported that a common side effect of translation-blocking morpholino antisense oligonucleotides is the induction of a set of innate immune response genes in Xenopus embryos and that splicing-blocking morpholinos lead to unexpected off-target mis-splicing events. Here, we present an analysis of al...

    journal_title:Developmental cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.devcel.2019.04.019

    authors: Paraiso KD,Blitz IL,Zhou JJ,Cho KWY

    更新日期:2019-05-20 00:00:00

  • Fate mapping embryonic blood in zebrafish: multi- and unipotential lineages are segregated at gastrulation.

    abstract::Vertebrate hematopoiesis first produces primitive (embryonic) lineages and ultimately generates the definitive (adult) blood. Whereas definitive hematopoiesis may produce many diverse blood types via a common multipotent progenitor, primitive hematopoiesis has been thought to produce only erythrocytes or macrophages v...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2009.04.007

    authors: Warga RM,Kane DA,Ho RK

    更新日期:2009-05-01 00:00:00

  • The PAR-6 polarity protein regulates dendritic spine morphogenesis through p190 RhoGAP and the Rho GTPase.

    abstract::The majority of excitatory synaptic transmission in the brain occurs at dendritic spines, which are actin-rich protrusions on the dendrites. The asymmetric nature of these structures suggests that proteins regulating cell polarity might be involved in their formation. Indeed, the polarity protein PAR-3 is required for...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2007.11.020

    authors: Zhang H,Macara IG

    更新日期:2008-02-01 00:00:00

  • Transcriptional Heterogeneity of Beta Cells in the Intact Pancreas.

    abstract::Pancreatic beta cells have been shown to be heterogeneous at multiple levels. However, spatially interrogating transcriptional heterogeneity in the intact tissue has been challenging. Here, we developed an optimized protocol for single-molecule transcript imaging in the intact pancreas and used it to identify a sub-po...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2018.11.001

    authors: Farack L,Golan M,Egozi A,Dezorella N,Bahar Halpern K,Ben-Moshe S,Garzilli I,Tóth B,Roitman L,Krizhanovsky V,Itzkovitz S

    更新日期:2019-01-07 00:00:00

  • Reciprocal regulation between resting microglial dynamics and neuronal activity in vivo.

    abstract::Microglia are the primary immune cells in the brain. Under physiological conditions, they typically stay in a "resting" state, with ramified processes continuously extending to and retracting from surrounding neural tissues. Whether and how such highly dynamic resting microglia functionally interact with surrounding n...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2012.10.027

    authors: Li Y,Du XF,Liu CS,Wen ZL,Du JL

    更新日期:2012-12-11 00:00:00

  • Ozz-E3, a muscle-specific ubiquitin ligase, regulates beta-catenin degradation during myogenesis.

    abstract::The identities of the ubiquitin-ligases active during myogenesis are largely unknown. Here we describe a RING-type E3 ligase complex specified by the adaptor protein, Ozz, a novel SOCS protein that is developmentally regulated and expressed exclusively in striated muscle. In mice, the absence of Ozz results in overt m...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/s1534-5807(04)00020-6

    authors: Nastasi T,Bongiovanni A,Campos Y,Mann L,Toy JN,Bostrom J,Rottier R,Hahn C,Conaway JW,Harris AJ,D'Azzo A

    更新日期:2004-02-01 00:00:00

  • Lipid Droplets Are Essential for Efficient Clearance of Cytosolic Inclusion Bodies.

    abstract::Exposing cells to folding stress causes a subset of their proteins to misfold and accumulate in inclusion bodies (IBs). IB formation and clearance are both active processes, but little is known about their mechanism. To shed light on this issue, we performed a screen with over 4,000 fluorescently tagged yeast proteins...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2015.04.015

    authors: Moldavski O,Amen T,Levin-Zaidman S,Eisenstein M,Rogachev I,Brandis A,Kaganovich D,Schuldiner M

    更新日期:2015-06-08 00:00:00

  • E2F3-a novel repressor of the ARF/p53 pathway.

    abstract::The Arf tumor suppressor is a key component of the p53 tumor surveillance pathway, and its expression is activated by abnormal proliferation signals. In a recent paper, Lees and coworkers investigate the regulation of Arf expression by E2Fs and demonstrate that in normal cells E2F3 is a pivotal repressor of Arf. ...

    journal_title:Developmental cell

    pub_type: 评论,杂志文章,评审

    doi:10.1016/j.devcel.2004.05.012

    authors: Ginsberg D

    更新日期:2004-06-01 00:00:00

  • The bacterial cytoskeleton: in vivo dynamics of the actin-like protein Mbl of Bacillus subtilis.

    abstract::Mbl is a bacterial actin homolog that controls cell morphogenesis in Bacillus subtilis. A functional GFP-Mbl fusion protein was used to examine the behavior of the helical cables formed by Mbl protein in live B. subtilis cells. The cables undergo dynamic changes during cell cycle progression. They are stable but not r...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/s1534-5807(02)00403-3

    authors: Carballido-López R,Errington J

    更新日期:2003-01-01 00:00:00

  • ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development.

    abstract::Cell polarity plays a key role in the development of the central nervous system (CNS). Interestingly, disruption of cell polarity is seen in many cancers. ASPP2 is a haplo-insufficient tumor suppressor and an activator of the p53 family. In this study, we show that ASPP2 controls the polarity and proliferation of neur...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2010.06.003

    authors: Sottocornola R,Royer C,Vives V,Tordella L,Zhong S,Wang Y,Ratnayaka I,Shipman M,Cheung A,Gaston-Massuet C,Ferretti P,Molnár Z,Lu X

    更新日期:2010-07-20 00:00:00

  • An essential role for 14-3-3 proteins in brassinosteroid signal transduction in Arabidopsis.

    abstract::Brassinosteroids (BRs) are essential hormones for plant growth and development. BRs regulate gene expression by inducing dephosphorylation of two key transcription factors, BZR1 and BZR2/BES1, through a signal transduction pathway that involves cell-surface receptors (BRI1 and BAK1) and a GSK3 kinase (BIN2). How BR-re...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2007.06.009

    authors: Gampala SS,Kim TW,He JX,Tang W,Deng Z,Bai MY,Guan S,Lalonde S,Sun Y,Gendron JM,Chen H,Shibagaki N,Ferl RJ,Ehrhardt D,Chong K,Burlingame AL,Wang ZY

    更新日期:2007-08-01 00:00:00

  • Retroviral genomic RNAs are transported to the plasma membrane by endosomal vesicles.

    abstract::The viral genomes of alpha- and gamma-retroviruses follow an outbound route through the cytoplasm before assembling with the budding particle at the plasma membrane. We show here that murine leukemia virus (MLV) RNAs are transported on lysosomes and transferrin-positive endosomes. Transport on transferrin-positive ves...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/s1534-5807(03)00188-6

    authors: Basyuk E,Galli T,Mougel M,Blanchard JM,Sitbon M,Bertrand E

    更新日期:2003-07-01 00:00:00

  • Translational repression of cyclin E prevents precocious mitosis and embryonic gene activation during C. elegans meiosis.

    abstract::Germ cells, the cells that give rise to sperm and egg, maintain the potential to recreate all cell types in a new individual. This wide developmental potential, or totipotency, is manifested in unusual tumors called teratomas, in which germ cells undergo somatic differentiation. Although recent studies have implicated...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2009.08.003

    authors: Biedermann B,Wright J,Senften M,Kalchhauser I,Sarathy G,Lee MH,Ciosk R

    更新日期:2009-09-01 00:00:00

  • Coordinating proliferation and tissue specification to promote regional identity in the Drosophila head.

    abstract::The Decapentaplegic and Notch signaling pathways are thought to direct regional specification in the Drosophila eye-antennal epithelium by controlling the expression of selector genes for the eye (Eyeless/Pax6, Eyes absent) and/or antenna (Distal-less). Here, we investigate the function of these signaling pathways in ...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/s1534-5807(03)00243-0

    authors: Kenyon KL,Ranade SS,Curtiss J,Mlodzik M,Pignoni F

    更新日期:2003-09-01 00:00:00

  • Human SEIPIN Binds Anionic Phospholipids.

    abstract::The biogenesis of lipid droplets (LDs) and the development of adipocytes are two key aspects of mammalian fat storage. SEIPIN, an integral membrane protein of the endoplasmic reticulum (ER), plays a critical role in both LD formation and adipogenesis. The molecular function of SEIPIN, however, has yet to be elucidated...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2018.09.010

    authors: Yan R,Qian H,Lukmantara I,Gao M,Du X,Yan N,Yang H

    更新日期:2018-10-22 00:00:00

  • MOR23 promotes muscle regeneration and regulates cell adhesion and migration.

    abstract::Odorant receptors (ORs) in the olfactory epithelium bind to volatile small molecules leading to the perception of smell. ORs are expressed in many tissues but their functions are largely unknown. We show multiple ORs display distinct mRNA expression patterns during myogenesis in vitro and muscle regeneration in vivo. ...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2009.09.004

    authors: Griffin CA,Kafadar KA,Pavlath GK

    更新日期:2009-11-01 00:00:00

  • From blood to brain: the neurogenic niche of the crayfish brain.

    abstract::Adult neurogenic niches are present in both vertebrates and invertebrates. Where do stem cells populating these niches originate, and what are the mechanisms maintaining their self-renewal? In this issue of Developmental Cell, Benton et al. (2014) show that in crayfish, hemolymph-derived cells enter a neurogenic niche...

    journal_title:Developmental cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.devcel.2014.07.024

    authors: Hartenstein V

    更新日期:2014-08-11 00:00:00

  • Probing intrinsic properties of a robust morphogen gradient in Drosophila.

    abstract::A remarkable feature of development is its reproducibility, the ability to correct embryo-to-embryo variations and instruct precise patterning. In Drosophila, embryonic patterning along the anterior-posterior axis is controlled by the morphogen gradient Bicoid (Bcd). In this article, we describe quantitative studies o...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2008.09.004

    authors: He F,Wen Y,Deng J,Lin X,Lu LJ,Jiao R,Ma J

    更新日期:2008-10-01 00:00:00

  • The γ-secretase cleavage product of polycystin-1 regulates TCF and CHOP-mediated transcriptional activation through a p300-dependent mechanism.

    abstract::Mutations in Pkd1, encoding polycystin-1 (PC1), cause autosomal-dominant polycystic kidney disease (ADPKD). We show that the carboxy-terminal tail (CTT) of PC1 is released by γ-secretase-mediated cleavage and regulates the Wnt and CHOP pathways by binding the transcription factors TCF and CHOP, disrupting their intera...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2011.10.028

    authors: Merrick D,Chapin H,Baggs JE,Yu Z,Somlo S,Sun Z,Hogenesch JB,Caplan MJ

    更新日期:2012-01-17 00:00:00

  • The POU domain protein spg (pou2/Oct4) is essential for endoderm formation in cooperation with the HMG domain protein casanova.

    abstract::The gastrulating vertebrate embryo develops three germlayers: ectoderm, mesoderm, and endoderm. Zebrafish endoderm differentiation starts with the activation of sox17 by casanova (cas). We report that spg (pou2/Oct4) is essential for endoderm formation. Embryos devoid of maternal and zygotic spg function (MZspg) lack ...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/s1534-5807(03)00396-4

    authors: Reim G,Mizoguchi T,Stainier DY,Kikuchi Y,Brand M

    更新日期:2004-01-01 00:00:00

  • GATA/Heme Multi-omics Reveals a Trace Metal-Dependent Cellular Differentiation Mechanism.

    abstract::By functioning as an enzyme cofactor, hemoglobin component, and gene regulator, heme is vital for life. One mode of heme-regulated transcription involves amplifying the activity of GATA-1, a key determinant of erythrocyte differentiation. To discover biological consequences of the metal cofactor-transcription factor m...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2018.07.022

    authors: Tanimura N,Liao R,Wilson GM,Dent MR,Cao M,Burstyn JN,Hematti P,Liu X,Zhang Y,Zheng Y,Keles S,Xu J,Coon JJ,Bresnick EH

    更新日期:2018-09-10 00:00:00

  • Dynamic Control of Enhancer Repertoires Drives Lineage and Stage-Specific Transcription during Hematopoiesis.

    abstract::Enhancers are the primary determinants of cell identity, but the regulatory components controlling enhancer turnover during lineage commitment remain largely unknown. Here we compare the enhancer landscape, transcriptional factor occupancy, and transcriptomic changes in human fetal and adult hematopoietic stem/progeni...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2015.12.014

    authors: Huang J,Liu X,Li D,Shao Z,Cao H,Zhang Y,Trompouki E,Bowman TV,Zon LI,Yuan GC,Orkin SH,Xu J

    更新日期:2016-01-11 00:00:00

  • Genomic analysis of gastrulation and organogenesis in the mouse.

    abstract::We developed a comprehensive dataset that samples the mouse transcriptome every 6 hr, from gastrulation through organogenesis. We observe an abrupt increase in overall transcript diversity at the onset of organogenesis (e8.0); the genes that comprise these changes are preferentially clustered along chromosome 7 and co...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2007.10.004

    authors: Mitiku N,Baker JC

    更新日期:2007-12-01 00:00:00

  • Cyclin C: an inducer of mitochondrial division hidden in the nucleus.

    abstract::In response to cellular stress, mitochondria remodel their structure by organelle division and fusion. In this issue of Developmental Cell, Cooper et al. (2014) report that a nuclear protein, cyclin C, is recruited from nuclei to mitochondria upon oxidative stress and promotes mitochondrial division and apoptosis of t...

    journal_title:Developmental cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.devcel.2014.01.010

    authors: Adachi Y,Sesaki H

    更新日期:2014-01-27 00:00:00

  • Pioneering barren land: mitotic bookmarking by transcription factors.

    abstract::Genome condensation during mitosis presents a chromatin landscape largely inaccessible to RNA polymerase II and most transcription factors. Caravaca et al. (2013) now report in Genes and Development that the pioneer transcription factor FOXA1 is retained at mitotic chromosomes, bookmarking the genome to enable gene ex...

    journal_title:Developmental cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.devcel.2013.02.005

    authors: Rada-Iglesias A

    更新日期:2013-02-25 00:00:00

  • Moving right along: how PP1 helps clear the checkpoint.

    abstract::Spindle checkpoint silencing is crucial for cell-cycle progression, but mechanisms underlying this process remain mysterious. Two papers, one in this issue of Developmental Cell (Meadows et al., 2011) and one in Current Biology (Rosenberg et al., 2011), begin to show how phosphatase PP1-gamma connects chromosome-micro...

    journal_title:Developmental cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.devcel.2011.05.017

    authors: Maldonado M,Kapoor TM

    更新日期:2011-06-14 00:00:00

  • Spreading the silence.

    abstract::RITS (RNA-induced initiation of transcriptional gene silencing complex) plays diverse roles in heterochromatin regulation: silencing transcription by recruitment of chromatin modifiers and destroying transcripts by RNAi. In a recent issue of Molecular Cell, Li et al. now show that the polymerization of Tas3, a compone...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2009.05.002

    authors: Partridge JF

    更新日期:2009-05-01 00:00:00

  • Foxf2 Is Required for Brain Pericyte Differentiation and Development and Maintenance of the Blood-Brain Barrier.

    abstract::Pericytes are critical for cerebrovascular maturation and development of the blood-brain barrier (BBB), but their role in maintenance of the adult BBB, and how CNS pericytes differ from those of other tissues, is less well understood. We show that the forkhead transcription factor Foxf2 is specifically expressed in pe...

    journal_title:Developmental cell

    pub_type: 杂志文章

    doi:10.1016/j.devcel.2015.05.008

    authors: Reyahi A,Nik AM,Ghiami M,Gritli-Linde A,Pontén F,Johansson BR,Carlsson P

    更新日期:2015-07-06 00:00:00

  • Autophagosome formation: tracing the source.

    abstract::Although it is well appreciated that autophagy begins with phagophore formation and expansion through lipid acquisition to become the autophagosome, this process remains poorly understood, with the source of autophagosome membrane controversial. Reporting recently in Nature, Hamasaki et al. (2013) suggest that the ER-...

    journal_title:Developmental cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.devcel.2013.04.004

    authors: Bernard A,Klionsky DJ

    更新日期:2013-04-29 00:00:00

  • T-box time in England.

    abstract::T-box genes encode DNA binding transcription factors known to regulate a wide variety of developmental processes during embryogenesis and are present in the genomes of all multicellular animals. Indeed, alongside other more familiar families of developmental regulators such as Hox, Sox, and Pax, T-box genes constitute...

    journal_title:Developmental cell

    pub_type:

    doi:10.1016/s1534-5807(02)00330-1

    authors: Gibson-Brown JJ

    更新日期:2002-11-01 00:00:00