Kinectin participates in microtubule-dependent hormone secretion in pancreatic islet beta-cells.
Kinectin (KNT) is a candidate membrane receptor for kinesin in the movement of intracellular organelles along microtubules. Isoforms of KNT exist containing different combinations of six small (residues 23-33) variable domains (vd) vd1-6 within the C-terminus. Here we investigate a role for KNT and its isoform KNTvd4(-) in the transport of amylin and insulin-containing secretory vesicles in the pancreatic islet beta-cell line RINm5F. KNTvd4(-) lacks vd4 that forms the kinesin-binding domain, and hence its role in the cell is an enigma. We report that amylin-containing vesicles also contained insulin, and exhibited microtubule, and small G-protein-dependent secretion. Knockdown of KNT by small interference RNA (siRNA) inhibited amylin expression and secretion. In contrast, recombinant KNTvd4(-) overexpressed in RINm5F cells associated with amylin-containing vesicles and inhibited amylin secretion, but had no discernible affect on amylin expression. The data suggests that both KNT and KNTvd4(-) participate in microtubule-dependent secretion of amylin in islet beta-cells.
Bai
Ji-Zhong
JZ
Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Mon
Yu
Y
Krissansen
Geoffrey W
GW
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D003594:Cytoplasmic Granules / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D058228:Islet Amyloid Polypeptide; D016547:Kinesins / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D034622:RNA Interference; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; C088547:KTN1 protein, human; D008565:Membrane Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D016547:Kinesins