A role for Rab10 in von Willebrand factor release discovered by an AP‐1 interactor screen in C. elegans

Michaux, Grégoire; Dyer, Clare E. F.; Nightingale, Thomas D.; Gallaud, Emmanuel; Nurrish, Stephen; Cutler, Daniel F.

doi:10.1111/j.1538-7836.2010.04138.x

Cited by 15 publications

(11 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An RNAi screen in C. elegans for defective transport vesicle adaptor complex 1 component AP-1 showed that rab-10 is important for von Willebrand factor secretion [52]. Here we present the first in vivo studies in a multicellular model organism showing that exoc-7 and exoc-8 are functionally linked to the small GTPase rab-10 .…”

Section: Discussionmentioning

confidence: 80%

Exocyst Subunits Exo70 and Exo84 Cooperate with Small GTPases to Regulate Behavior and Endocytic Trafficking in C. elegans

et al. 2012

View full text Add to dashboard Cite

The exocyst complex is required for cell polarity regulation and the targeting and tethering of transport vesicles to the plasma membrane. The complex is structurally well conserved, however, the functions of individual subunits and their regulation is poorly understood. Here we characterize the mutant phenotypes for the exocyst complex genes exoc-7 (exo70) and exoc-8 (exo84) in Caenorhabditis elegans. The mutants display pleiotropic behavior defects that resemble those observed in cilia mutants (slow growth, uncoordinated movement, defects in chemo-, mechano- and thermosensation). However, no obvious morphological defects in cilia were observed. A targeted RNAi screen for small GTPases identified eleven genes with enhanced phenotypes when combined with exoc-7, exoc-8 single and exoc-7;exoc-8 double mutants. The screen verified previously identified functional links between the exocyst complex and small GTPases and, in addition, identified several novel potential regulators of exocyst function. The exoc-8 and exoc-7;exoc-8 mutations caused a significant size increase in the rab-10 RNAi-induced endocytic vacuoles in the intestinal epithelial cells. In addition, exoc-8 and exoc-7;exoc-8 mutations resulted in up-regulation of RAB-10 expression and affected the accumulation of endocytic marker proteins in these cells in response to rab-10 RNAi. The findings identify novel, potential regulators for exocyst function and show that exoc-7 and exoc-8 are functionally linked to rab-10 in endosomal trafficking in intestinal epithelial cells in C. elegans.

show abstract

Section: Discussionmentioning

confidence: 80%

Exocyst Subunits Exo70 and Exo84 Cooperate with Small GTPases to Regulate Behavior and Endocytic Trafficking in C. elegans

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Because Slp4-a can also bind Rab8 and Rab3A-3D 15,21 (and supplemental Figure 4A), we next looked for the expression and WPB localization of these Rab proteins. Although HUVECs express Rab8, 11,29 we detected neither endogenous nor epitope-tagged Rab8 …”

Section: Slp4-a Is Localized To Wpbsmentioning

confidence: 72%

The interplay between the Rab27A effectors Slp4-a and MyRIP controls hormone-evoked Weibel-Palade body exocytosis

Bierings

Hellen

Kiskin

et al. 2012

Blood

166

View full text Add to dashboard Cite

Weibel-Palade body (WPB) exocytosis underlies hormone-evoked VWF secretion from endothelial cells (ECs). We identify new endogenous components of the WPB: Rab3B, Rab3D, and the Rab27A/ Rab3 effector Slp4-a (granuphilin), and determine their role in WPB exocytosis. We show that Rab3B, Rab3D, and Rab27A contribute to Slp4-a localization to WPBs. siRNA knockdown of Slp4-a, MyRIP, Rab3B, Rab3D, Rab27A, or Rab3B/ Rab27A, or overexpression of EGFPSlp4-a or EGFP-MyRIP showed that Slp4-a is a positive and MyRIP a negative regulator of WPB exocytosis and that Rab27A alone mediates these effects. We found that ECs maintain a constant amount of cellular Rab27A irrespective of the WPB pool size and that Rab27A (and Rab3s) cycle between WPBs and a cytosolic pool. The dynamic redistribution of Rab proteins markedly decreased the Rab27A concentration on individual WPBs with increasing WPB number per cell. Despite this, the probability of WPB release was independent of WPB pool size showing that WPB exocytosis is not determined simply by the absolute amount of Rab27A and its effectors on WPBs. Instead, we propose that the probability of release is determined by the fractional occupancy of WPB-Rab27A by Slp4-a and MyRIP, with the balance favoring exocytosis. (Blood. 2012;120(13):2757-2767) IntroductionHormone-evoked VWF secretion from endothelial cells (ECs) is mediated by exocytosis of specialized secretory granules (SGs) called Weibel-Palade bodies (WPBs). 1 WPB exocytosis is triggered by increases in intracellular free Ca 2ϩ or cAMP concentrations, and involves a number of molecular components, including the Nethylmaleimide-sensitive factor, VAMP3, SNAP23, syntaxin 4, RalA, the annexin A2/S100A10 complex, and phospholipase D. [2][3][4][5][6][7] In addition, Rab proteins also regulate WPB exocytosis. A subset of Rab proteins, including Rab3A-3D, Rab27A/B, and Rab37, is associated with SGs in different cell types where they regulate SG biogenesis, trafficking, and exocytosis. 8 Secretory cells often express a mixture of these "secretory" Rabs, which may have overlapping or distinct functions. Human ECs are reported to express mRNA for Rab3A, Rab3D, and Rab37,3,9,10 Rab3B protein, 11 and Rab27A mRNA and protein. 12,13 To date, Rab27A is the only endogenous EC Rab protein that has been detected on WPBs. Through its effector MyRIP and Myosin Va, Rab27A is proposed to negatively regulate WPB exocytosis. 13,14 Rab27A can interact with different effector molecules, and many secretory cells express a mixture of these effectors. 8 In these cases, SG exocytosis probably depends on the balance of Rab27A interactions with the complement of Rab effectors in the cell.In addition to MyRIP, ECs contain mRNA for the Rab27A effector Slp4-a (granuphilin). 13 Slp4-a links SGs to the plasma membrane (PM) through SG-associated Rab proteins (principally Rab27A), PM-associated syntaxins (1a, 2, or 3) and soluble Munc18 isoforms. [15][16][17][18][19] Syntaxins exist in open and closed conformations that determine their participation in SNARE complex f...

show abstract

“…Studies in the C. elegans intestine show a crucial function for Rab11 and the clathrin adaptor AP1 in promoting apical polarization (Michaux et al 2011;Shafaq-Zadah et al 2012). AP1 is specifically required for the formation of apical Rab11 vesicles and for the apical localization of Cdc42 and the polarity determinant PAR-6, similar to their role in MDCK cell polarization.…”

Section: Transcytosis and Apical Lumen Morphogenesis In Polarized Epimentioning

confidence: 95%

Cargo Sorting in the Endocytic Pathway: A Key Regulator of Cell Polarity and Tissue Dynamics

Eaton

Martı́n-Belmonte

2014

Cold Spring Harbor Perspectives in Biology

View full text Add to dashboard Cite

The establishment and maintenance of polarized plasma membrane domains is essential for cellular function and proper development of organisms. Epithelial cells polarize along two fundamental axes, the apicobasal and the planar, both depending on finely regulated protein trafficking mechanisms. Newly synthesized proteins destined for either surface domain are processed along the biosynthetic pathway and segregated into distinct subsets of transport carriers emanating from the trans-Golgi network or endosomes. This exocytic trafficking has been identified as essential for proper epithelial polarization. Accumulating evidence now reveals that endocytosis and endocytic recycling play an equally important role in epithelial polarization and the appropriate localization of key polarity proteins. Here, we review recent work in metazoan systems illuminating the connections between endocytosis, postendocytic trafficking, and cell polarity, both apicobasal and planar, in the formation of differentiated epithelial cells, and how these processes regulate tissue dynamics. ENDOCYTOSIS REGULATES APICOBASAL EPITHELIAL POLARITY

show abstract

A role for Rab10 in von Willebrand factor release discovered by an AP‐1 interactor screen in C. elegans

Cited by 15 publications

References 50 publications

Exocyst Subunits Exo70 and Exo84 Cooperate with Small GTPases to Regulate Behavior and Endocytic Trafficking in C. elegans

Exocyst Subunits Exo70 and Exo84 Cooperate with Small GTPases to Regulate Behavior and Endocytic Trafficking in C. elegans

The interplay between the Rab27A effectors Slp4-a and MyRIP controls hormone-evoked Weibel-Palade body exocytosis

Cargo Sorting in the Endocytic Pathway: A Key Regulator of Cell Polarity and Tissue Dynamics

Contact Info

Product

Resources

About