Effects of BIG1 and KANK1 on cell polarity and directed migration during wound healing

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NHLBI	CELLBIO-12

Authors

• C-C Li
• J-K Kuo
• R Kiyama
• J Moss
• M Vaughan

Abstract

Brefeldin A-inhibited guanine nucleotide-exchange protein (BIG)1 activates class I ADP-ribosylation factors by accelerating the replacement of bound GDP with GTP to initiate recruitment of coat proteins for membrane vesicle formation. Among proteins that interact with BIG1, kinesin family member 21A (KIF21A), a plus-end-directed motor protein, moves cargo away from the microtubule-organizing center (MTOC) on microtubules. Here, we describe a newly recognized relationship between BIG1 and KANK1, a protein that has multiple actions in cells and interacts with KIF21A. Overexpressed KANK1 appeared partially colocalized with endogenous BIG1, consistent with potentially functional interactions as was their reciprocal immunoprecipitation (IP), but direct interaction of KANK1 and BIG1 was not established. Depletion or overexpression BIG1 protein appeared not to affect KANK1 distribution. Effects of BIG1- and KANK1-depletion on cell migration in wound-healing assays were, however, remarkably similar. Depletion of BIG1 or KANK1 interfered significantly with directed cell migration and initial orientation of Golgi/MTOC toward the leading edge, but KIF21A depletion did not have such effects. These studies identify novel functions of both BIG1 and KANK1 in regulating cell polarity during directed migration.

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