RESP18, a homolog of the luminal domain IA-2, is found in dense core vesicles in pancreatic islet cells and is induced by high glucose.
The regulated endocrine-specific protein, RESP18, first found in the rat pituitary, was thought to be regulated by dopaminergic drugs. Bioinformatics studies showed that RESP18 shares sequence homology with the luminal region of IA-2, a dense core vesicle (DCV) transmembrane protein involved in insulin secretion. The present study was initiated to examine the genomic structure and subcellular localization of RESP18 and the effect of glucose on its expression. Human RESP18 was isolated from a pancreas cDNA library and its subcellular localization was determined by immunoelectron microscopy. MIN6 cells and mouse islets were used to study the effect of glucose on RESP18 expression. Bioinformatics analysis revealed that RESP18 and IA-2 are tandemly arranged within a 45 kb region on human chromosome 2 and share common intron-exon boundaries. By confocal microscopy, RESP18 was found in alpha, beta and delta cells in the pancreatic islets. Electron microscopy revealed that RESP18 is present in the lumen of DCVs. The expression of RESP18 in beta cells is markedly increased following exposure to high glucose and also elevated in the islets of diabetic, but not non-diabetic, NOD mice. We conclude that RESP18 is a luminal protein of DCVs and its expression is regulated by exposure to glucose.
Zhang
Guofeng
G
Experimental Medicine Section, Oral Infection and Immunity Branch (OIIB), National Institute of Dental and Craniofacial Research (NIDCR), The National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
Hirai
Hiroki
H
Cai
Tao
T
Miura
Junnosuke
J
Yu
Ping
P
Huang
Hanxia
H
Schiller
Martin R
MR
Swaim
William D
WD
Leapman
Richard D
RD
Notkins
Abner L
AL
D000818:Animals; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D019295:Computational Biology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019143:Evolution, Molecular; D015894:Genome, Human; D005947:Glucose / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007340:Insulinoma / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000235:genetics / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution; D015854:Up-Regulation
D009419:Nerve Tissue Proteins; C086381:regulated endocrine secretory protein 18; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005947:Glucose