65 Oral - Cell Division and Cell Growth
Friday April 08, 9:45 AM - 10:00 AM

Late Endosomes act as carriers for delivery of Ceramide phosphoethanolamine (CPE) with unique acyl chain anchors to cleavage furrows during male meiosis cytokinesis.


Authors:
Govind Kunduri 1; Si-Hung Le 2; Baena Valentina 3; Nagampalli Vijaykrishna 4; Daniel Blankenberg 4; Yoshihiro, Izumi 2; Takeshi Bamba 2; Kedar Narayan 3; Usha Acharya 1; Jaira Acharya 1

Affiliations:
1) Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute; 2) Department of Metabolomics, Kyushu University; 3) Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute; 4) Genomic Medicine Institute and Lerner Research Institute, Cleveland Clinic, Cleveland

Keywords:
b. meiosis; l. endosomes

Cell division, wherein one cell divides into two daughter cells, is fundamental to all living organisms. Cytokinesis, the final step of cell division, begins with the formation of an actomyosin contractile ring, positioned midway between the segregated chromosomes. Constriction of the ring with concomitant membrane addition in a spatiotemporal manner generates a cleavage furrow that physically separates the cytoplasm. Unique lipids with specific biophysical properties have been shown to localize to midbodies, however, their delivery mechanisms and biological roles remain largely unknown. In this study, we show that Ceramide phosphoethanolamine (CPE), the structural analog of sphingomyelin, has unique acyl chain anchors in spermatocytes and is essential for meiosis cytokinesis. The head group of CPE is also important for spermatogenesis. We found aberrant central spindle and contractile ring behavior but not de-localization of phosphatidyl inositols (PIPs) at the plasma membrane was responsible for the male meiosis cytokinesis defect in CPE deficient animals. Further, we demonstrate the enrichment of CPE in Rab7 and Rab11 positive endosomes which in turn translocate to the cleavage furrows to promote cytokinesis. Volume electron microscopy analysis using Correlative light and focused ion beam scanning electron microscopy showed that CPE enriched Rab7 positive endosomes appear as giant, interconnected multivesicular bodies that are juxtaposed on contractile ring material. Genetic ablation of Rab7 alone results in significant meiotic cytokinesis defects. Our results imply endosomal delivery of CPE to ingressing membranes is crucial for male meiotic cytokinesis.