TY - JOUR
T1 - PI3K regulates endocytosis after insulin secretion by mediating signaling crosstalk between Arf6 and Rab27a
AU - Yamaoka, Mami
AU - Ando, Tomomi
AU - Terabayashi, Takeshi
AU - Okamoto, Mitsuhiro
AU - Takei, Masahiro
AU - Nishioka, Tomoki
AU - Kaibuchi, Kozo
AU - Matsunaga, Kohichi
AU - Ishizaki, Ray
AU - Izumi, Tetsuro
AU - Niki, Ichiro
AU - Ishizaki, Toshimasa
AU - Kimura, Toshihide
PY - 2016
Y1 - 2016
N2 - 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 (PIP3) 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.
AB - 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 (PIP3) 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.
UR - http://www.scopus.com/inward/record.url?scp=84957613348&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84957613348&partnerID=8YFLogxK
U2 - 10.1242/jcs.180141
DO - 10.1242/jcs.180141
M3 - Article
C2 - 26683831
AN - SCOPUS:84957613348
SN - 0021-9533
VL - 129
SP - 637
EP - 649
JO - Journal of cell science
JF - Journal of cell science
IS - 3
ER -