The SNARE Machinery Is Involved in Apical Plasma Membrane Trafficking in MDCK Cells

Low, Seng Hui; Chapin, Steven J.; Wimmer, Christian; Whiteheart, Sidney W.; Kömüves, László G.; Mostov, Keith E.; Weimbs, Thomas

doi:10.1083/jcb.141.7.1503

Cited by 170 publications

(180 citation statements)

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“…Regulation of cell fate by αSnap may affect other organs, but previous analysis has not shown hypoplasia of other organs 1 in hyh mice, perhaps because other tissues regulate size postnatally, whereas the postnatal brain contains largely postmitotic neurons. Other genes that affect the size of the central nervous system in humans commonly do not affect other organs, even when they are ubiquitously expressed 27,28 29 , analysis of the hyh mutant supports this role and provides an opportunity to examine the role of apical vesicle trafficking in other aspects of neural development. The hyh mutant has additional defects in cerebellar development, neuronal migration and axonal pathfinding (data not shown), suggesting roles for apical trafficking in these processes.…”

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confidence: 87%

The hyh mutation uncovers roles for αSnap in apical protein localization and control of neural cell fate

et al. 2004

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The hyh (hydrocephalus with hop gait) mouse shows a markedly small cerebral cortex at birth and dies postnatally from progressive enlargement of the ventricular system 1,2 . Here we show that the small hyh cortex reflects altered cell fate. Neural progenitor cells withdraw prematurely from the cell cycle, producing more early-born, deep-layer cerebral cortical neurons but depleting the cortical progenitor pool, such that late-born, upper-layer cortical neurons are underproduced, creating a small cortex. hyh mice carry a hypomorphic missense mutation in the gene Napa encoding soluble N-ethylmaleimidesensitive factor (NSF) attachment protein alpha (αSnap), involved in SNAP receptor (SNARE)-mediated vesicle fusion in many cellular contexts. A targeted null Napa mutation is embryonically lethal. Altered neural cell fate is accompanied by abnormal localization of many apical proteins implicated in regulation of neural cell fate, including E-cadherin, β-catenin, atypical protein kinase C (aPKC) and INADL (inactivation-noafterpotential D-like, also known as protein associated with Lin7, or Pals1). Apical localization of the SNARE Vamp7 is also disrupted. Thus, αSnap is essential for apical protein localization and cell fate determination in neuroepithelial cells.

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confidence: 87%

The hyh mutation uncovers roles for αSnap in apical protein localization and control of neural cell fate

et al. 2004

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“…The EPP has adapted these universal trafficking mechanisms to the task of generating different apical and basolateral transporters and delivering them to their respective PM domains. Docking of apical transporters depends on the T-SNARE syntaxin 3 in MDCK cells (Low et al, 1996) and on a tetanus-insensitive V-SNARE (Galli et al, 1998;Low et al, 1998;Lafont et al, 1999). Docking of basolateral transporters requires syntaxin 4 (Low et al, 1996), rab 8 (Huber et al, 1993) and a V-SNARE, cellubrevin, which cooperates with AP-1B in basolateral membrane trafficking (Fields et al, 2007), as well as the exocyst (Grindstaff et al, 1998;Shipitsin and Feig, 2004; The EPP: machineries involved and their hijacking by cancer B Tanos and E Rodriguez-Boulan Yeaman et al, 2004b;Langevin et al, 2005), a multiprotein particle that is also a key regulator of yeast's secretory route (Potenza et al, 1992;TerBush and Novick, 1995;TerBush et al, 1996).…”

Section: Polarized Trafficking Machinerymentioning

confidence: 99%

The epithelial polarity program: machineries involved and their hijacking by cancer

2008

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The Epithelial Polarity Program (EPP) adapts and integrates three ancient cellular machineries to construct an epithelial cell. The polarized trafficking machinery adapts the cytoskeleton and ancestral secretory and endocytic machineries to the task of sorting and delivering different plasma membrane (PM) proteins to apical and basolateral surface domains. The domain-identity machinery builds a tight junctional fence (TJ) between apical and basolateral PM domains and adapts ancient polarity proteins and polarity lipids on the cytoplasmic side of the PM, which have evolved to perform a diversity of polarity tasks across cells and species, to provide 'identity' to each epithelial PM domain. The 3D organization machinery utilizes adhesion molecules as positional sensors of other epithelial cells and the basement membrane and small GTPases as integrators of positional information with the activities of the domain-identity and polarized trafficking machineries. Cancer is a disease mainly of epithelial cells (90% of human cancers are carcinomas that derive from epithelial cells) that hijacks the EPP machineries, resulting in loss of epithelial polarity, which often correlates in extent with the aggressiveness of the tumor. Here, we review how the EPP integrates its three machineries and the strategies used by cancer to hijack them.

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“…This pattern has been observed in numerous epithelial cell types, suggesting that it may reflect a fundamental aspect of the roles of syx3 and 4 in specific traffic. Syx3 is involved in TGN to AP traffic, whereas syx4 has been implicated in TGN to BL traffic (Low et al, 1998;Lafont et al, 1999). The existence of branching pathways from the TGN to AP or BL surface makes epithelial cells a particularly fortuitous system for studying the role of syntaxins in the specificity of vesicle fusion.…”

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The Role of Syntaxins in the Specificity of Vesicle Targeting in Polarized Epithelial Cells

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Chapin

Avrahami

et al. 2005

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In polarized epithelial cells syntaxin 3 is at the apical plasma membrane and is involved in delivery of proteins from the trans-Golgi network to the apical surface. The highly related syntaxin 4 is at the basolateral surface. The complementary distribution of these syntaxins suggests that they play a role in the specificity of membrane traffic to the two surfaces. We constructed a chimeric syntaxin where we removed the N-terminal 29 residues of syntaxin 3 and replaced it with the corresponding portion of syntaxin 4. When expressed in polarized epithelial cells, this chimera was exclusively localized to the basolateral surface. This indicates that the N-terminal domain of syntaxin 3 contains information for its polarized localization. In contrast to the apical localization of syntaxin 3, the basolateral localization of syntaxin 4 was not dependent on its N-terminal domain. Syntaxin 3 normally binds to Munc18b, but not to the related Munc18c. Overexpression of the chimera together with overexpression of Munc18b caused membrane and secretory proteins that are normally sent primarily to the apical surface to exhibit increased delivery to the basolateral surface. We suggest that syntaxins may play a role in determining the specificity of membrane targeting by permitting fusion with only certain target membranes. INTRODUCTIONEukaryotic cells contain numerous intracellular membranous compartments that are connected by vesicular traffic. After vesicles bud off from a membrane, they must be targeted to and fuse with the correct target membrane. How vesicles are specifically targeted to the correct membrane and avoid fusion with the incorrect membrane remains a paramount question (Mostov et al., 2003;Nelson, 2003;Rodriguez-Boulan et al., 2005). Several classes of molecules may contribute to this specificity and it is possible that specificity is conferred by multiple layers of molecular machinery, which may act sequentially. For instance, at least in larger animal cells, vesicles may first reach the vicinity of their target membrane by using motor proteins and cytoskeletal filaments. Thus, some of the specificity may be achieved by binding and activation of the correct motor protein to the vesicle. In many trafficking steps, vesicles are then brought closer to the membrane by tethering complexes. For instance, the yeast exocyst and its homologous mammalian sec6/8 complex tether vesicles to the specific locations on the plasma membrane (Lipschutz and Mostov, 2002;Novick and Guo, 2002).SNARE proteins act later and may catalyze fusion itself (Sollner, 2003;Ungar and Hughson, 2003;Jahn, 2004). The original formulation of the SNARE hypothesis postulated that specific v-SNARES on the vesicle paired with cognate t-SNAREs on the target, thereby providing specificity to fusion (Sollner et al., 1993). This premise was challenged when SNARE proteins, lacking their membrane anchors, were produced. Soluble versions of v-and t-SNARES paired almost completely promiscuously, suggesting that pairing of specific SNAREs did not contribute ...

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The SNARE Machinery Is Involved in Apical Plasma Membrane Trafficking in MDCK Cells

Cited by 170 publications

References 54 publications

The hyh mutation uncovers roles for αSnap in apical protein localization and control of neural cell fate

The hyh mutation uncovers roles for αSnap in apical protein localization and control of neural cell fate

The epithelial polarity program: machineries involved and their hijacking by cancer

The Role of Syntaxins in the Specificity of Vesicle Targeting in Polarized Epithelial Cells

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