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Scientists uncover a novel mechanism for de novo polarity establishment

Updated: 2021-05-29

Sexual reproduction in animals requires the formation and fusion of two haploid gametes, sperm and oocyte, to generate a diploid offspring. Sperm from males must be activated or capacitated on the right time and right place in order to achieve fertilization success. Sperm activation is a process whereby round and still spermatids differentiate into asymmetric and motile spermatozoa without the transcriptional and translational modification. The molecular mechanism underlying this de novo symmetry-breaking process, however, remains largely unknown.


In a study published online in Developmental Cell on May 28, Dr. MIAO Long's team at the Institute of Biophysics, Chinese Academy of Sciences, revealed that during nematode C. elegans sperm activation, Na+/K+-ATPase (also known as Na+/K+ pump), which is initially present on the plasma membrane (PM), moves centripetally toward cell body and subsequently enters the fusion pore in the cell body. The polarization of Na+/K+ pump depends on the transport of cholesterol from the PM to intracellular membranous organelles (MOs) via membrane contact sites (MCSs).


C. elegans sperm contain relatively few organelles, namely a haploid nucleus, mitochondria, and MOs. In the late stage of sperm activation, the MO membrane fuses with the PM, leaving a permanent invagination on the cell body surface. The researchers found that MOs are apposed at approximately 10 nm to the PM, which indicates that MOs may form MCSs with the PM. There is increasing evidence that MCSs are formed by tether proteins between tightly apposed membranes of diverse organelles, including the PM. The MCSs provide an efficient platform for lipid and ion transfer between distinct organelles in a non-vesicular manner. The researchers revealed that in C. elegans sperm, cholesterol is evenly distributed on the PM and is highly enriched in MOs. During sperm activation, Na+/K+ pump and cholesterol transport on the PM is correlated. Specifically, both Na+/K+ pump and cholesterol are similarly sorted and transported against their concentration gradients during sperm activation. Cholesterol moves from the PM to MOs against its concentration gradient through the MCSs stably formed between MOs and the PM. The association between the PI4P phosphatase SAC-1 and MOs implies that the localized PI4P hydrolysis on the PM catalyzed in trans by SAC-1 may provide the energy required for transporting cholesterol from the PM to MOs. A phosphoinositide 5-phosphatase, CIL-1, which preferentially converts PI(4,5)P2 to PI4P, may regulate PI4P biosynthesis, which in turn maintains the driving force to modulate cholesterol trafficking and Na+/K+ pump translocation during sperm activation. This study implies that lipid transfer at MCSs might facilitate the translocation of ion channels and transporters to modulate cell polarity establishment and cell motility acquisition. Further studies on MOs in C. elegans sperm, for example, investigations on the molecular compositions of MOs and mechanism of MOs formation, will provide implications for elucidating functions of lipid homeostasis and lipid transfer proteins in regulating membrane dynamics and organelle interactions in other cell types.


This study was supported by the National Key Research and Development Program of China and National Natural Science Foundation of China.



Polarization of Na+/K+ pump from the spermatid surface to the rear portion of the spermatozoon cell body during C. elegans sperm activation (Video by MIAO Long's group)


Fulltext link: https://www.cell.com/developmental-cell/fulltext/S1534-5807(21)00402-0


Contact: MIAO Long

Institute of Biophysics, Chinese Academy of Sciences

Beijing 100101, China

Email: lmiao@ibp.ac.cn


(Reported by Dr. MIAO Long's group)




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