HKRP3 is a microtubule-binding protein regulating lytic granule clustering and NK cell killing

Hyoungjun Ham, Walter Huynh, Renee A. Schoon, Ronald D. Vale, Daniel D Billadeau

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

NK cells provide host defense by killing viral-infected and cancerous cells through the secretion of preformed lytic granules. Polarization of the lytic granules toward the target cell is dependent on an intact microtubule (MT) network as well as MT motors.We have recently shown that DOCK8, a gene mutated in a primary immunodeficiency syndrome, is involved in NK cell killing in part through its effects on MTorganizing center (MTOC) polarization. In this study, we identified Hook-related protein 3 (HkRP3) as a novel DOCK8- and MT-binding protein. We further show that HkRP3 is present in lytic granule fractions and interacts with the dynein motor complex and MTs. Significantly, depletion of HkPR3 impaired NK cell cytotoxicity, which could be attributed to a defect in not only MTOC polarity, but also impaired clustering of lytic granules around the MTOC. Our results demonstrate an important role for HkRP3 in regulating the clustering of lytic granules and MTOC repositioning during the development of NK cell-mediated killing.

Original languageEnglish (US)
Pages (from-to)3984-3996
Number of pages13
JournalJournal of Immunology
Volume194
Issue number8
DOIs
StatePublished - Apr 15 2015

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ASJC Scopus subject areas

  • Immunology

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