The GDP-dependent Rab27a effector coronin 3 controls endocytosis of secretory membrane in insulin-secreting cell lines

Kimura, Toshihide; Kaneko, Yukiko; Yamada, S.; Ishihara, Hideharu; Senda, Toshiya; Iwamatsu, Akihiro; Niki, Ichiro

doi:10.1242/jcs.030544

Cited by 64 publications

(78 citation statements)

References 53 publications

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“…21,22) Surprisingly, coronin 3 selectively forms a complex with GDP-bound Rab27a but not with GTP-bound Rab27a. 20) This is consistent with the structure of coronin 3 in that it does not contain a synaptotagmin-like homology domain (SHD), a potential GTP-bound Rab27a binding site. 23) Coronin 3 also lacks a GDP dissociation inhibitor (GDI) consensus sequence.…”

Section: Coroninsupporting

confidence: 81%

GTP- and GDP-Dependent Rab27a Effectors in Pancreatic Beta-Cells

Yamaoka

Ishizaki

Kimura

2015

Biological & Pharmaceutical Bulletin

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Small guanosine triphosphatases (GTPases) participate in a wide variety of cellular functions including proliferation, differentiation, adhesion, and intracellular transport. Conventionally, only the guanosine 5′-triphosphate (GTP)-bound small GTPase interacts with effector proteins, and the resulting downstream signals control specific cellular functions. Therefore, the GTP-bound form is regarded as active, and the focus has been on searching for proteins that bind the GTP form to look for their effectors. The Rab family small GTPase Rab27a is highly expressed in some secretory cells and is involved in the control of membrane traffic. The present study reviews recent progress in our understanding of the roles of Rab27a and its effectors in pancreatic beta-cells. In the basal state, GTP-bound Rab27a controls insulin secretion at pre-exocytic stages via its GTP-dependent effectors. We previously identified novel guanosine 5′-diphosphate (GDP)-bound Rab27-interacting proteins. Interestingly, GDP-bound Rab27a controls endocytosis of the secretory membrane via its interaction with these proteins. We also demonstrated that the insulin secretagogue glucose converts Rab27a from its GTP-to GDP-bound forms. Thus, GTP-and GDP-bound Rab27a regulate pre-exocytic and endocytic stages in membrane traffic, respectively. Since the physiological importance of GDP-bound GTPases has been largely overlooked, we consider that the investigation of GDP-dependent effectors for other GTPases is necessary for further understanding of cellular function.

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Section: Coroninsupporting

confidence: 81%

GTP- and GDP-Dependent Rab27a Effectors in Pancreatic Beta-Cells

Yamaoka

Ishizaki

Kimura

2015

Biological & Pharmaceutical Bulletin

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“…37 Unlike for Rab3s, conversion to GDP-Rab27A is not associated with loss from membranes. 37 Whether this arises because Rab27A is a poor substrate for GDI or because access to GDI is hindered by binding to effectors in the GDP-state (eg, Slp4-a, coronin-3) 41,42 remains to be established. The cycling of EGFP-Slp4-a on mRFP-Rab27A-expressing WPBs mirrored the very slow cycling of Rab27A itself, presumably because Slp4-a, unlike other Rabs, binds to both GTP and GDP-bound states of Rab27A.…”

Section: Slp4-a Recruitment To Wpbsmentioning

confidence: 99%

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

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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...

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“…Interestingly however, loss of NHA2 had no impact on the endosomal steady-state pH in β-cells. Exocytosis and endocytosis were shown to be tightly coupled in β-cells [126,100] and inhibition of endocytosis by various approaches reduced insulin secretion [75,105]. Loss of NHA2 therefore may affect insulin secretion indirectly by interfering with clathrin-mediated endocytosis in β-cells, thereby disrupting endo-exocytosis coupling.…”

Section: Slc9b or Nha Familymentioning

confidence: 99%

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Fuster

Alexander

2013

Pflugers Arch - Eur J Physiol

144

122

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The SLC9 gene family encodes Na + /H + exchangers (NHEs). These transmembrane proteins transport ions across lipid bilayers in a diverse array of species from prokaryotes to eukaryotes, including plants, fungi and animals. They utilize the electrochemical gradient of one ion to transport another ion against its electrochemical gradient. Currently, 13 evolutionarily conserved NHE isoforms are known in mammals [46,22,128]. The SLC9 gene family (solute carrier classification of transporters:www.bioparadigms.org) is divided into three subgroups [46]. The SLC9A subgroup encompasses plasmalemmal isoforms NHE1-5 (SLC9A1-5) and the predominantly intracellular isoforms NHE6-9 (SLC9A6-9). The SLC9B subgroup consists of two recently cloned isoforms, NHA1 and NHA2 (SLC9B1 and SLC9B2, respectively). The SLC9C subgroup consist of a sperm specific plasmalemmal NHE (SLC9C1) and a putative NHE, SLC9C2, for which there is currently no functional data [46].NHEs participate in the regulation of cytosolic and organellar pH as well as cell volume. In the intestine and kidney, NHEs are critical for transepithelial movement of Na + and HCO 3 -and thus for whole body volume and acid-base homeostasis [46]. Mutations in the NHE6 or NHE9 genes cause neurological disease in humans and are currently the only NHEs directly linked to human disease.However, it is becoming increasingly apparent that members of this gene family contribute to the pathophysiology of multiple human diseases.

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The GDP-dependent Rab27a effector coronin 3 controls endocytosis of secretory membrane in insulin-secreting cell lines

Cited by 64 publications

References 53 publications

GTP- and GDP-Dependent Rab27a Effectors in Pancreatic Beta-Cells

GTP- and GDP-Dependent Rab27a Effectors in Pancreatic Beta-Cells

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

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

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