Cell cycle-dependent palmitoylation of protocadherin 7 by ZDHHC5 promotes successful cytokinesis.

Cell division requires dramatic reorganization of the cell cortex which is primarily driven by the actomyosin network. We previously reported that Protocadherin 7 (PCDH7) gets enriched at the cell surface during mitosis which is required to build up the full mitotic rounding pressure. Here we report that PCDH7 interacts with, and is palmitoylated by the palmitoyltransferase, ZDHHC5. Both PCDH7 and ZDHHC5 co-localize at the mitotic cell surface, and translocate to the cleavage furrow during cytokinesis. PCDH7's localization depends on the palmitoylation activity of ZDHHC5. Silencing PCDH7 increases the percentage of multinucleated cells and the duration of mitosis. Loss of PCDH7 expression correlates with reduced levels of active RhoA and phospho-myosin at the cleavage furrow. This work uncovers a palmitoylation-dependent translocation mechanism for PCDH7 which contributes to the reorganization of the cortical cytoskeleton during cell division.