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A Chaperon‐Like Protein HYPK Binds Arl4 Small GTPases to Modulate Cell Migration
Author(s) -
Lee Fang-Jen Scott,
Lin Ming-Chieh
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09598
Subject(s) - huntingtin , microbiology and biotechnology , gtpase , guanine nucleotide exchange factor , gene knockdown , chemistry , chaperone (clinical) , small gtpase , golgi apparatus , rac1 , adp ribosylation factor , cell migration , phenotype , mutant , cell , signal transduction , biology , apoptosis , gene , biochemistry , medicine , pathology
ADP‐ribosylation factor (Arf)‐like 4 proteins are a group of small GTPases that control actin remodeling and promote cell migration. Their expression is finely tuned during development and only detectable in specific tissues. Dysregulation of Arl4s is linked with several cancers but little investigation reveals how they are regulated. Here we identified huntingtin yeast two‐hybrid protein K (HYPK) as a novel interacting partner of Arl4A and Arl4D, but not Arl4C. HYPK, primarily known as huntingtin (Htt) interacting protein, is reported to reduce aggregates and apoptosis induced by Htt and exhibited chaperone‐like activity. We show that HYPK interacts with Arl4A/D and modulates Arl4A/D‐dependent cellular phenotypes and cell migration ability. Arl4A/D does not appear to involve in HYPK‐mediated reduction of Htt aggregation. Residues 115–129 within C‐terminal conserved domain, possessing chaperon‐like activity of HYPK, is required and sufficient to interact with Arl4A/D. Losing of HYPK nullifies Arl4A‐induced cell migration, and only WT, but not Arl4A‐binding‐defective HYPK mutant, can rescue this phenotype. In addition, Arl4A exhibits reduced plasma membrane signals and its ability to maintain trans‐Golgi integrity in HYPK knockdown cells. Taken together, we infer that HYPK may serve as an upstream modulator of Arl4A/D to confer function of Arl4 small GTPases. Support or Funding Information This work was supported by grants from the National Health Research Institutes (NHRI) in Taiwan (NHRI‐EX106‐10601B1)