ZDHHC5 directs Protocadherin 7 to the mitotic cell surface and cleavage furrow by a palmitoylation-dependent mechanism for a successful cell division

Abstract

ABSTRACTCell division requires dramatic reorganization of the cell cortex that is primarily driven by the actomyosin network. We previously reported that Protocadherin 7 (PCDH7) enriches at the cell surface during mitosis which is required for building up the full mitotic rounding pressure. Here we showed that PCDH7 gets palmitoylated and interacts with the palmitoyltransferase, ZDHHC5. Both PCDH7 and ZDHHC5 co-localize at the mitotic cell surface and get enriched at the cleavage furrow during cytokinesis. PCDH7’s localization is ZDHHC5 dependent. Loss of expression of ZDHHC5 or PCDH7 leads to defects in cleavage furrow ingression and cytokinesis. At the mitotic cell surface and cleavage furrow, PCDH7 interacts with Myosin Phosphatase Target Subunit1 (MYPT1). We propose that this interaction tunes phospho-myosin levels at the cleavage furrow for regulating the myosin activity during cytokinesis. This work uncovers a palmitoylation-dependent translocation for PCDH7 which regulates myosin activity at the cortex and cleavage furrow for a successful division in human cells.