Kinesins in Mammalian Spermatogenesis and Germ Cell Transport

Abstract

In mammalian testes, the apical cytoplasm of each Sertoli cell holds up to several dozens of germ cells, especially spermatids that are transported up and down the seminiferous epithelium. The blood-testis barrier (BTB) established by neighboring Sertoli cells in the basal compartment restructures on a regular basis to allow preleptotene/leptotene spermatocytes to pass through. The timely transfer of germ cells and other cellular organelles such as residual bodies, phagosomes, and lysosomes across the epithelium to facilitate spermatogenesis is important and requires the microtubule-based cytoskeleton in Sertoli cells. Kinesins, a superfamily of the microtubule-dependent motor proteins, are abundantly and preferentially expressed in the testis, but their functions are poorly understood. This review summarizes recent findings on kinesins in mammalian spermatogenesis, highlighting their potential role in germ cell traversing through the BTB and the remodeling of Sertoli cell-spermatid junctions to advance spermatid transport. The possibility of kinesins acting as a mediator and/or synchronizer for cell cycle progression, germ cell transit, and junctional rearrangement and turnover is also discussed. We mostly cover findings in rodents, but we also make special remarks regarding humans. We anticipate that this information will provide a framework for future research in the field.

Keywords: apical ectoplasmic specialization; blood-testis barrier; cell junctions; cytoskeleton; kinesin; sertoli cells; spermatogenesis; testis.

FIGURE 1

(A) A schematic diagram depicting the basic structure of a kinesin motor (B) Three representative kinesins (kinesin-1,-2, and -3) bearing cargoes traveling on microtubule (MT) tracks, with their specific molecular structures shown. KLC, kinesin light chain; KHC, kinesin heavy chain; KAP, kinesin associated protein; FHA, forkhead associated domain.

FIGURE 2

The domain structure and classifications of kinesins discovered in each of the human, mouse, and rat genomes (except that KIF16A and KIF19B are predictive in the rat). KIF11 is also known as KIF8 in the mouse, and KIF6 is also known as kinesin-related protein 3 (KRP3) in the rat. KIFC1 has isoforms KIFC4 and KIFC5 in the mouse. Kinesins share a common structure but also have domains that are unique to each KIF member. KLC, kinesin light chain; KHC, kinesin heavy chain; TPR, tetratricopeptide repeat; WD40 repeats, protein interaction motifs of approximately 40 amino acids that usually terminate in tryptophan-aspartic acid (WD); FHA, forkhead associated; PH, Pleckstrin homology; CAP-Gly, cytoskeleton-associated protein glycine-rich; PX, PhoX homologous; HhH1, Helix-hairpin-Helix DNA-binding motif class 1.

FIGURE 3

(Left) A diagram depicting the cell cycle progression and different germ cell types during spermatogenesis. (Right) A schematic drawing that illustrates the cross section of the seminiferous tubule in the rat testis. Four types of Sertoli cell-cell junctions at the blood-testis barrier (BTB), namely tight junction (TJ), basal ectoplasmic specialization, gap junction (GJ), and desmosome, as well as cell-cell junctions at the Sertoli-germ cell interface are illustrated. Spermatogonia, spermatocytes, and steps 1–7 round spermatids are connected to Sertoli cells via GJ/desmosome. More advanced spermatids (steps 8 and later) are connected to Sertoli cells via apical ectoplasmic specialization. The BTB, which is created by two adjacent Sertoli cells, divides the seminiferous epithelium into two compartments: adluminal and basal. At stage VIII of the epithelial cycle, the “new” BTB forms before the “old” BTB disassembles to allow the transport of preleptotene/leptotene spermatocytes. Also, near the seminiferous tubule lumen, apical ectoplasmic specialization disassembles to release the elongated spermatids during spermiation. The apical ectoplasmic specialization is hypothesized to be associated with microtubule (MT)-based motors (kinesins and dyneins) that allow “down and up” movement in the apical seminiferous epithelium of maturing spermatids.