Leucine zipper protein 1 (LUZP1) regulates the constriction velocity of the contractile ring during cytokinesis

• Published in: The FEBS journal 2024-03, Vol.291 (5), p.927-944
• Main Authors: Hyodo, Toshinori, Asano‐Inami, Eri, Ito, Satoko, Sugiyama, Mai, Nawa, Akihiro, Rahman, Md Lutfur, Hasan, Muhammad Nazmul, Mihara, Yuko, Lam, Vu Quang, Karnan, Sivasundaram, Ota, Akinobu, Tsuzuki, Shinobu, Hamaguchi, Michinari, Hosokawa, Yoshitaka, Konishi, Hiroyuki
• Format: Article
• Language: English
• Subjects: Actin; Actin Cytoskeleton; Anaphase; Cell division; chromosomal passenger complex; Constriction; Constrictions; Contractility; Cytokinesis; Cytokinesis - genetics; Cytoskeleton; Kinases; Kinesin; Leucine; leucine zipper protein 1; Leucine zipper proteins; Leucine Zippers; Mass spectrometry; Mass spectroscopy; Metaphase; Mitosis; Myosin; Phosphorylation; Proteins; siRNA; Substrate inhibition; Velocity
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.17017

There has been a great deal of research on cell division and its mechanisms; however, its processes still have many unknowns. To find novel proteins that regulate cell division, we performed the screening using siRNAs and/or the expression plasmid of the target genes and identified leucine zipper protein 1 (LUZP1). Recent studies have shown that LUZP1 interacts with various proteins and stabilizes the actin cytoskeleton; however, the function of LUZP1 in mitosis is not known. In this study, we found that LUZP1 colocalized with the chromosomal passenger complex (CPC) at the centromere in metaphase and at the central spindle in anaphase and that these LUZP1 localizations were regulated by CPC activity and kinesin family member 20A (KIF20A). Mass spectrometry analysis identified that LUZP1 interacted with death‐associated protein kinase 3 (DAPK3), one regulator of the cleavage furrow ingression in cytokinesis. In addition, we found that LUZP1 also interacted with myosin light chain 9 (MYL9), a substrate of DAPK3, and comprehensively inhibited MYL9 phosphorylation by DAPK3. In line with a known role for MYL9 in the actin‐myosin contraction, LUZP1 suppression accelerated the constriction velocity at the division plane in our time‐lapse analysis. Our study indicates that LUZP1 is a novel regulator for cytokinesis that regulates the constriction velocity of the contractile ring. Cell division is a complex process with tight spatial and temporal regulation. Our screen identified leucine zipper protein 1 (LUZP1) as a key mediator of contractile ring dynamics during cell division. Like the chromosomal passenger complex (CPC), LUZP1 localizes at the inner centromere in metaphase and at the central spindle in anaphase. LUZP1 controls the phosphorylation of MYL9 by DAPK3, and this control depends on how LUZP1 interacts with these proteins. In line with the known role for MYL9 in actin‐myosin contraction, LUZP1 modulates the constriction velocity of the contractile ring in cytokinesis.