JSAP 1 and JLP are required for ARF 6 localization to the midbody in cytokinesis

• Published in: Genes to cells : devoted to molecular & cellular mechanisms Vol. 19; no. 9; pp. 692 - 703
• Main Authors: Tuvshintugs, Baljinnyam, Sato, Tokiharu, Enkhtuya, Radnaa, Yamashita, Katsumi, Yoshioka, Katsuji
• Format: Journal Article
• Language: English
• Published: 01-09-2014
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/gtc.12170

The
ADP
‐ribosylation factor 6 (
ARF
6)
GTP
ase is important in cytokinesis and localizes to the midbody. However, the mechanism and regulation of
ARF
6's recruitment to the midbody are largely unknown. Here, we investigated the functions of two binding partners of active
ARF
6, c‐Jun
NH
2
‐terminal kinase (
JNK
)/stress‐activated protein kinase‐associated protein 1 (
JSAP
1) and
JNK
‐associated leucine zipper protein (
JLP
), by gene knockout and rescue experiments in mouse embryonic fibroblasts. Depleting both
JSAP
1 and
JLP
impaired
ARF
6's localization to the midbody and delayed cytokinesis. These defects were almost completely rescued by wild‐type
JSAP
1 or
JLP
, but not by
JSAP
1 or
JLP
mutants that were unable to interact with active
ARF
6 or with the kinesin heavy chain (
KHC
) of kinesin‐1. In transfected cells, a constitutively active form of
ARF
6 associated with
KHC
only when co‐expressed with wild‐type
JSAP
1 or
JLP
and not with a
JSAP
1 or
JLP
mutant. These findings suggest that
JSAP
1 and
JLP
, which might be paralogous to each other, are critical and functionally redundant in cytokinesis and control
ARF
6 localization to the midbody by forming a tripartite complex of
JSAP
1/
JLP
, active
ARF
6, and kinesin‐1.