Human spermatogenesis leads to a reduced nuclear pore structure and function

Nuclear pore complexes (NPCs) are nuclear gateways which regulate transit of molecules larger than 40kDa through a Ran-dependent transport. The somatic human NPC scaffold consists of three stacked rings: cytoplasmic, nucleoplasmic, and inner ring, which define an approximately 55nm-wide central channel. However, how NPC architecture accommodates the different function of non-somatic cells is largely unknown.

Here, we reveal the in-cell architecture of the human sperm NPC exhibiting a central channel less than 40nm-wide, outlined exclusively by the inner ring. This is accompanied by a 6-fold reduction in nuclear diffusion and mis-localization of Ran-dependent transport components. We also unveil a septin filaments meshwork connecting the NPCs and postulate a mechanical role in channel constriction. Furthermore, we show the end of meiosis as the key differentiation step for NPC architectural changes.

Our work uses an integrative approach comprising electron-cryo-tomography, super-resolution-light-microscopy and biochemistry, to investigate macromolecular structure/ function in human physiological contexts.