Activated Cdc42-Bound IQGAP1 Determines the Cellular Endocytic Site

Kimura, Toshihide; Yamaoka, Mami; Taniguchi, Shigeki; Okamoto, Mitsuhiro; Takei, Masahiro; Ando, Tomomi; Iwamatsu, Akihiro; Watanabe, Takashi; Kaibuchi, Kozo; Ishizaki, Toshimasa; Niki, Ichiro

doi:10.1128/mcb.00895-13

Cited by 33 publications

(41 citation statements)

References 47 publications

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“…These interactions are important for the transport and tethering of insulin granules. We recently identified coronin 3 (also known as CORO1C) and IQGAP1 as new Rab27a-interacting proteins (Kimura et al, 2008(Kimura et al, , 2013. In contrast to previously established small GTPase interactors, these proteins selectively form a complex with the GDP-bound, but not with the GTP-bound, Rab27a.…”

Section: Introductionmentioning

confidence: 98%

“…We have demonstrated previously that GDP-bound Rab27a promotes glucose-induced clathrin-dependent endocytosis through its interaction with coronin 3 and IQGAP1 (Kimura et al, 2008(Kimura et al, , 2013. We therefore examined the effect of the crosstalk between EPI64 and ARNO signaling on endocytosis.…”

Section: Arno Is Required For the Glucose-induced Translocation Of Epi64mentioning

confidence: 99%

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PI3K regulates endocytosis after insulin secretion by mediating signaling crosstalk between Arf6 and Rab27a

Yamaoka

Ando

Terabayashi

et al. 2016

Journal of Cell Science

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In secretory cells, endocytosis is coupled to exocytosis to enable proper secretion. Although endocytosis is crucial to maintain cellular homeostasis before and after secretion, knowledge about secretagogue-induced endocytosis in secretory cells is still limited. Here, we searched for proteins that interacted with the Rab27a GTPase-activating protein (GAP) EPI64 (also known as TBC1D10A) and identified the Arf6 guanine-nucleotide-exchange factor (GEF) ARNO (also known as CYTH2) in pancreatic β-cells. We found that the insulin secretagogue glucose promotes phosphatidylinositol (3,4,5)-trisphosphate (PIP 3 ) generation through phosphoinositide 3-kinase (PI3K), thereby recruiting ARNO to the intracellular side of the plasma membrane. Peripheral ARNO promotes clathrin assembly through its GEF activity for Arf6 and regulates the early stage of endocytosis. We also found that peripheral ARNO recruits EPI64 to the same area and that the interaction requires glucose-induced endocytosis in pancreatic β-cells. Given that GTP-and GDP-bound Rab27a regulate exocytosis and the late stage of endocytosis, our results indicate that the glucose-induced activation of PI3K plays a pivotal role in exocytosis-endocytosis coupling, and that ARNO and EPI64 regulate endocytosis at distinct stages.

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Section: Introductionmentioning

confidence: 98%

Section: Arno Is Required For the Glucose-induced Translocation Of Epi64mentioning

confidence: 99%

PI3K regulates endocytosis after insulin secretion by mediating signaling crosstalk between Arf6 and Rab27a

Yamaoka

Ando

Terabayashi

et al. 2016

Journal of Cell Science

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“…[34][35][36][37][38][39][40] We recently identified IQGAP1 as another GDP-dependent Rab27a effector. 41) GDP-bound Rab27a interacts with IQGAP1 via its RasGAP related domain (GRD). This domain is a part of the GTP-bound Cdc42-binding region of IQGAP1.…”

Section: Iq Motif Containing Gtpase Activating Protein 1 (Iqgap1)mentioning

confidence: 99%

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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“…Studies on β-cells have revealed that IQGAP1 recruits the endocytic machinery to the plasma membrane together with GTP-bound Cdc42 [125] and that IQGAP1-exocystseptin enhanced exocytosis is inhibited by Cdc42 [126]. In adherens junction fractions from rat liver Rac-Cdc42-IQGAP1 was shown to inhibit the clathrin-dependent (caveolae-independent) endocytosis of E-cadherin, probably through cross-linking of Factin [127].…”

Section: Iqgap1 and The Cytoskeletonmentioning

confidence: 99%

Human Adipocytes : Proteomic Approaches

Jufvas¹

2016

Linköping University Medical Dissertations

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Type 2 diabetes is characterized by increased levels of glucose in the blood originating from insulin resistance in insulin sensitive tissues and from reduced pancreatic insulin production. Around 400 million people in the world are diagnosed with type 2 diabetes and the correlation with obesity is strong. In addition to life style induction of obesity and type 2 diabetes, there are indications of genetic and epigenetic influences. This thesis has focused on the characterization of primary human adipocytes, who play a crucial role in the development of type 2 diabetes. Histones are important proteins in chromatin dynamics and may be one of the factors behind epigenetic inheritance. In paper I, we characterized histone variants and posttranslational modifications in human adipocytes. Several of the specific posttranslational histone modifications we identified have been characterized in other cell types, but the majority was not previously known. Moreover, we identified a variant of histone H4 on protein level for the first time. In paper II, we studied specific histone H3 methylations in the adipocytes. We found that overweight is correlated with a reduction of H3K4me2 while type 2 diabetes is associated with an increase of H3K4me3. This shows a genome-wide difference in important chromatin modifications that could help explain the epidemiologically shown association between epigenetics and metabolic health. Caveolae is a plasma membrane structure involved in the initial and important steps of insulin signaling. In paper III we characterized the IQGAP1 interactome in human adipocytes and suggest that IQGAP1 is a link between caveolae and the cytoskeleton. Moreover, the amount of IQGAP1 is drastically lower in adipocytes from type 2 diabetic subjects compared with controls implying a potential role for IQGAP1 in insulin resistance. In conclusion, this thesis provides new insights into the insulin signaling frameworks and the histone variants and modifications of human adipocytes

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Activated Cdc42-Bound IQGAP1 Determines the Cellular Endocytic Site

Cited by 33 publications

References 47 publications

PI3K regulates endocytosis after insulin secretion by mediating signaling crosstalk between Arf6 and Rab27a

PI3K regulates endocytosis after insulin secretion by mediating signaling crosstalk between Arf6 and Rab27a

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

Human Adipocytes : Proteomic Approaches

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