HAP1 helps to regulate actin-based transport of insulin-containing granules in pancreatic β cells

Histochemistry and Cell Biology
Zhiyong WangHe Li

Abstract

Huntingtin-associated protein 1 (HAP1) is enriched in neurons and binds to polyglutamine-expanded huntingtin. It consists of two alternatively spliced isoforms, HAP1A and HAP1B, which differ only in their short C-terminal sequences. Both HAP1A and HAP1B have been also detected in pancreatic β cells, where the loss of HAP1 impairs glucose-stimulated insulin secretion. Here, we use time-lapse laser scanning confocal microscopy to provide direct evidence that HAP1A, but not HAP1B, co-localizes and co-migrates with insulin-containing vesicles and actin-based myosin Va motor protein in the INS-1 pancreatic β cell line. Knocking down HAP1 expression using small interfering RNA significantly inhibited actin-based transport of insulin vesicles following glucose stimulation. Co-immunoprecipitation experiments demonstrated interaction between HAP1A, myosin Va, and phogrin, a transmembrane protein in insulin-containing vesicles. Stimulating INS-1 cells with glucose increased the association of HAP1A with myosin Va, while silencing HAP1 expression reduced the association of myosin Va with phogrin after glucose stimulation, without affecting levels of myosin Va or actin. Our results provide real-time evidence in living cells that HAP1 may h...Continue Reading

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Citations

Feb 18, 2016·Histochemistry and Cell Biology·Douglas J Taatjes, Jürgen Roth
Jan 5, 2020·Molecular Neurobiology·Jonathan Chang-Cheng ShiehYung-Feng Lin
Sep 15, 2016·The Journal of Biological Chemistry·Jing-Ying PanHe Li
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Sep 27, 2021·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·X ZhaoY Tao

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