Abstract：
:High-throughput neurotransmission at ribbon synapses of cochlear inner hair cells (IHCs) requires tight coupling of neurotransmitter release and balanced recycling of synaptic vesicles (SVs) as well as rapid restoration of release sites. Here, we examined the role of the adaptor protein AP180 (also known as SNAP91) for IHC synaptic transmission by comparing AP180-knockout (KO) and wild-type mice using high-pressure freezing and electron tomography, confocal microscopy, patch-clamp membrane capacitance measurements and systems physiology. AP180 was found predominantly at the synaptic pole of IHCs. AP180-deficient IHCs had severely reduced SV numbers, slowed endocytic membrane retrieval and accumulated endocytic intermediates near ribbon synapses, indicating that AP180 is required for clathrin-dependent endocytosis and SV reformation in IHCs. Moreover, AP180 deletion led to a high prevalence of SVs in a multi-tethered or docked state after stimulation, a reduced rate of SV replenishment and a hearing impairment. We conclude that, in addition to its role in clathrin recruitment, AP180 contributes to release site clearance in IHCs.This article has an associated First Person interview with the first author of the paper.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Kroll J,Özçete ÖD,Jung S,Maritzen T,Milosevic I,Wichmann C,Moser Tdoi
10.1242/jcs.236737subject
Has Abstractpub_date
2020-01-22 00:00:00issue
2eissn
0021-9533issn
1477-9137pii
jcs.236737journal_volume
133pub_type
杂志文章abstract：:The CHO1 antigen is a mitosis-specific kinesin-like motor located at the interzonal region of the spindle. The human cDNA coding for the antigen contains a domain with sequence similarity to the motor domain of kinesin-like protein (Nislow et al., Nature 359, 543, 1992). Here we cloned cDNAs encoding the CHO1 antigen ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:Previously, we documented the role of the programmed death-1 (PD-1, also known as PDCD1) pathway in macrophage apoptosis and the downregulation of this signaling during infection by the intra-macrophage parasite Leishmania donovani However, we also found that, during the late phase of infection, PD-1 expression was si...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.226274
更新日期：2019-05-02 00:00:00
abstract：:Fas ligand (FasL), a potent mediator of apoptosis expressed by CTL and NK cells, is sorted into the inner vesicles of secretory lysosomes for release via exosome-like vesicles. Previous studies identified a proline-rich domain in the cytoplasmic tail required for sorting FasL to secretory lysosomes, but the mechanisms...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03315
更新日期：2007-01-01 00:00:00
abstract：:Dynamin, a microtubule-activated GTPase, has recently been identified as the product of the shibire gene in Drosophila. shi(ts) mutants are defective in synaptic vesicle recycling, which leads to rapid and reversible temperature-sensitive paralysis. In the present study, results from RNase protection assays and analys...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1992-11-01 00:00:00
abstract：:The tandemly organised ribosomal DNA (rDNA) repeats are transcribed by a dedicated RNA polymerase in a specialised nuclear compartment, the nucleolus. There appears to be an intimate link between the maintenance of nucleolar structure and the presence of heterochromatic chromatin domains. This is particularly evident ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-12-01 00:00:00
abstract：:Rab proteins comprise a family of monomeric GTPases that control cellular membrane traffic. Rab21 is a poorly characterised member with no known function. Human Rab21 cDNA from K562 cells was subcloned into GFP expression vectors to generate Rab21 and Rab21 mutants defective in either GTP hydrolysis (Rab21 Q78L) or bi...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01560
更新日期：2004-12-15 00:00:00
abstract：:We show in the present study that homologs of hsp90 and hsp70 are induced by heat shocks in Tetrahymena and appear to form a high molecular mass complex (approximately 700 kDa) with tubulin. Three members of the hsp70 family (hsp72, 73, and 78) and one member of the hsp90 family (hsp82) have been identified by immunol...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1997-07-01 00:00:00
abstract：:We have previously reported that foetal and adult fibroblasts display distinctive migratory phenotypes when cultured on three-dimensional collagen gels. Both skin and tumour-derived fibroblasts from a significant proportion of patients with breast cancer were subsequently observed to display foetal-like migratory beha...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1988-07-01 00:00:00
abstract：:The specification of organs, tissues and cell types results from cell fate restrictions enacted by nuclear transcription factors under the control of conserved signaling pathways. The progenitor epithelium of the Drosophila compound eye, the eye imaginal disc, is a premier model for the study of such processes. Early ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.237834
更新日期：2020-05-26 00:00:00
abstract：:Misfolded endoplasmic reticulum (ER) proteins are dislocated towards the cytosol and degraded by the ubiquitin-proteasome system in a process called ER-associated protein degradation (ERAD). During infection with human cytomegalovirus (HCMV), the viral US2 protein targets HLA class I molecules (HLA-I) for degradation ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.206839
更新日期：2017-09-01 00:00:00
abstract：:The protein kinase inhibitor H-7 prevents the assembly of tight junctions in cultured Madin Darby Canine Kidney (MDCK) epithelial cells (Balda et al. (1991) J. Membr. Biol. 122, 193-202; Nigam et al. (1991) Biochem. Biophys. Res. Commun. 181, 548-553); however, its mechanism of action is unknown. To understand the bas...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-04-01 00:00:00
abstract：:Heparin-binding EGF-like growth factor (HB-EGF) is a ligand for EGF receptor (EGFR) and possesses the ability to signal in juxtacrine, autocrine and/or paracrine mode, with these alternatives being governed by the degree of proteolytic release of the ligand. Although the spatial range of diffusion of released HB-EGF i...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.058321
更新日期：2010-07-01 00:00:00
abstract：:The GGGGCC (G4C2) repeat expansion mutation in the C9ORF72 gene is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Transcription of the repeat and formation of nuclear RNA foci, which sequester specific RNA-binding proteins, is one of the possible pathological me...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.224303
更新日期：2019-03-07 00:00:00
abstract：:A synthetic gene encoding a 'consensus' calmodulin (synCaM) was able to substitute for the Saccharomyces cerevisiae calmodulin gene (CMDI), even though synCaM is only 60% identical in primary amino acid sequence to yeast Cmd1. Twelve different synCaM mutants were also expressed in yeast. Seven of the 12 mutant synCaMs...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
abstract：:Delayed wound healing caused by inefficient re-epithelialization underlines chronic skin lesions such as those found in diabetes. The dioxin receptor (AhR) modulates cell plasticity and migration and its activation by occupational polycyclic aromatic hydrocarbons (PAHs) results in severe skin lesions such as contact h...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.047274
更新日期：2009-06-01 00:00:00
abstract：:The assembly of an organism requires the interaction between different layers of cells, in many cases via an extracellular matrix. In the developing Drosophila larva, muscles attach in an integrin-dependent manner to the epidermis, via a specialized extracellular matrix called tendon matrix. Tiggrin, a tendon matrix i...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-11-01 00:00:00
abstract：:Members of the ezrin-radixin-moesin (ERM) family of proteins are involved in multiple aspects of cell migration by acting both as crosslinkers between the membrane, receptors and the actin cytoskeleton, and as regulators of signalling molecules that are implicated in cell adhesion, cell polarity and migration. Increas...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.133108
更新日期：2014-01-15 00:00:00
abstract：:It has been shown previously that whilst the rat type I integral membrane protein TGN38 (ratTGN38) is predominantly localised to the trans-Golgi network this protein does reach the cell surface from where it is internalised and delivered back to the trans-Golgi network. This protein thus provides a suitable tool for t...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-12-01 00:00:00
abstract：:The current model for hemoglobin ingestion and transport by intraerythrocytic Plasmodium falciparum malaria parasites shares similarities with endocytosis. However, the model is largely hypothetical, and the mechanisms responsible for the ingestion and transport of host cell hemoglobin to the lysosome-like food vacuol...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.023150
更新日期：2008-06-01 00:00:00
abstract：:The repair of injured tissue must occur rapidly to prevent microbial invasion and maintain tissue integrity. Epithelial tissues in particular, which serve as a barrier against the external environment, must repair efficiently in order to restore their primary function. Here we analyze the effect of different parameter...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.109066
更新日期：2012-12-15 00:00:00
abstract：:Drosophila Stardust (Sdt), a member of the MAGUK family of scaffolding proteins, is a constituent of the evolutionarily conserved Crumbs-Stardust (Crb-Sdt) complex that controls epithelial cell polarity in the embryo and morphogenesis of photoreceptor cells. Although apical localisation is a hallmark of the complex in...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.031088
更新日期：2008-06-15 00:00:00
abstract：:We first identified Bves (blood vessel/epicardial substance) as a transmembrane protein that localized to the lateral compartment of the epithelial epicardium. Bves traffics to sites of cell-cell contact in cultured epicardial cells and promotes adhesion following transfection into non-adherent fibroblastic L-cells, r...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02588
更新日期：2005-10-15 00:00:00
abstract：:The conformation and biological activities of fibronectin (FN) and vitronectin (VN) coated on different plastic surfaces were investigated using cell adhesion and a panel of domain-specific monoclonal antibodies (mAbs). The adhesion of BHK fibroblasts was markedly better on FN coated on hydrophilic tissue culture poly...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-03-01 00:00:00
abstract：:end13-1 was isolated in a screen for endocytosis mutants and has been shown to have a post-internalisation defect in endocytic transport as well as a defect in vacuolar protein sorting (Vps(-) phenotype), leading to secretion of newly synthesised vacuolar proteins. Here we demonstrate that END13 is identical to VPS4, ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-05-01 00:00:00
abstract：:DNA replication in eukaryotic cells initiates from multiple replication origins that are distributed throughout the genome. Coordinating the usage of these origins is crucial to ensure complete and timely replication of the entire genome precisely once in each cell cycle. Replication origins fire according to a cell-t...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.096701
更新日期：2013-03-15 00:00:00
abstract：:Nodal signaling induces the formation of the endoderm and mesoderm during gastrulation. Nodal expression persists until the definitive endoderm progenitor has completely formed, and disappears thereafter. A tightly regulated Nodal expression system is essential for the differentiation of embryonic stem (ES) cells into...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.004127
更新日期：2007-06-15 00:00:00
abstract：:Phosphoinositides regulate myriad cellular processes, acting as potent signaling molecules in conserved signaling pathways and as organelle gatekeepers that recruit effector proteins to membranes. Phosphoinositide-generating enzymes have been studied extensively in yeast and cultured cells, yet their roles in animal d...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.129031
更新日期：2014-03-01 00:00:00
abstract：:In fibroblasts, platelet-derived growth factor receptor alpha (PDGFRα) is upregulated during growth arrest and compartmentalized to the primary cilium. PDGF-AA mediated activation of the dimerized ciliary receptor produces a phosphorylation cascade through the PI3K-AKT and MEK1/2-ERK1/2 pathways leading to the activat...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.116426
更新日期：2013-02-15 00:00:00
abstract：:Micrographs were made of free-swimming hamster spermatozoa using a high intensity xenon flash and two-colour darkground illumination - conditions that permit three-dimensional reconstruction of the instantaneous shape of the flagellum. From the waveforms observed, we constructed an account of the three-dimensional kin...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1984-04-01 00:00:00
abstract：:Rap1 is a Ras-like small GTPase that is activated by many extracellular stimuli and strongly implicated in the control of integrin-mediated cell adhesion. Recent evidence indicates that Rap1 also plays a key role in formation of cadherin-based cell-cell junctions. Indeed, inhibition of Rap1 generates immature adherens...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.03306
更新日期：2007-01-01 00:00:00
