Membrane contact site-dependent cholesterol transport regulates Na+/K+-ATPase polarization and spermiogenesis in Caenorhabditis elegans.
Spermiogenesis in nematodes is a process whereby round and quiescent spermatids differentiate into asymmetric and crawling spermatozoa. The molecular mechanism underlying this symmetry breaking remains uncharacterized. In this study, we revealed that sperm-specific Na+/K+-ATPase (NKA) is evenly distributed on the plasma membrane (PM) of Caenorhabditis elegans spermatids but is translocated to and subsequently enters the invaginated membrane of the spermatozoa cell body during sperm activation. The polarization of NKA depends on the transport of cholesterol from the PM to membranous organelles (MOs) via membrane contact sites (MCSs). The inositol 5-phosphatase CIL-1 and the MO-localized PI4P phosphatase SAC-1 may mediate PI4P metabolism to drive cholesterol countertransport via sterol/lipid transport proteins through MCSs. Furthermore, the NKA function is required for C. elegans sperm motility and reproductive success. Our data imply that the lipid dynamics mediated by MCSs might play crucial roles in the establishment of cell polarity. eGraphical abstract.
['Wang|Qiushi|Q|', 'Cao|Zheng|Z|', 'Du|Baochen|B|', 'Zhang|Qi|Q|', 'Chen|Lianwan|L|', 'Wang|Xia|X|', 'Yuan|Zhiheng|Z|', 'Wang|Peng|P|', 'He|Ruijun|R|', 'Shan|Jin|J|', 'Zhao|Yanmei|Y|', 'Miao|Long|L|']
D000818:Animals D001692:Biological Transport D017173:Caenorhabditis elegans D029742:Caenorhabditis elegans Proteins D002784:Cholesterol D004950:Esterases D008297:Male D008565:Membrane Proteins D051336:Mitochondrial Membranes D015388:Organelles D000254:Sodium-Potassium-Exchanging ATPase D013081:Sperm Motility D013087:Spermatids D013091:Spermatogenesis D013094:Spermatozoa
cholesterol Na+/K+-ATPase sperm activation membrane contact sites C. elegans cell motility and cytoskeleton cell polarity establishment major sperm protein non-vesicular transport phospholipid