Internalization of Intact Intercellular Junctions in the Testis by Clathrin/Actin‐Mediated Endocytic Structures: Tubulobulbar Complexes

Abstract

Sertoli cells of the mammalian seminiferous epithelium form unique subcellular actin‐related structures at intercellular junctions. The appearance of these so called “tubulobulbar complexes” (TBCs) precedes both sperm release at the apex of the epithelium and the movement of early spermatogenic cells out of the spermatogonial stem cell niche at the base of the epithelium. TBCs are considered to be part of the mechanism of junction endocytosis by Sertoli cells. The structures contain junction proteins and morphologically identifiable junctions, and are associated with markers of endocytosis. Here we review the current state of knowledge about the structure and function of TBCs. As the complexes form, they morphologically resemble and have the molecular signature of clathrin‐coated pits with extremely long necks. As they mature, the actin filament networks around the “necks” of the structures progressively disassemble and the membrane cores expand or swell into distinct “bulbs”. These bulbs acquire extensive membrane contact sites with associated cisternae of endoplasmic reticulum. Eventually the bulbs undergo scission and continue through endosomal compartments of the Sertoli cells. The morphology and composition of TBC indicates to us that the structures likely evolved from the basic clathrin‐mediated endocytosis mechanism common to cells generally, and along the way they incorporated unique features to accommodate the cyclic turnover of massive and “intact” intercellular junctions that occurs during spermatogenesis. Anat Rec, 301:2080–2085, 2018. © 2018 Wiley Periodicals, Inc.

An actomyosin clamp assembled by the Amphiphysin-Rho1-Dia/DAAM-Rok pathway reinforces somatic cell membrane folded around spermatid heads

“…Hence, PIP 2 enrichment on the HCC membrane wrapped around the spermatid heads could promote Amph and Rho1 recruitment. Amph 1 along with a thick layer of F-actin and a multitude of actin-associated proteins are enriched on the tubular membrane of the TBCs found on the plasma membrane of the Sertoli cell that is bent around maturing spermatid heads (Adams et al, 2018;Kusumi et al, 2007). However, the role of Amph in the TBC formation in mammals is still unclear.…”

Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis

“…(for reviews, see ref. 8 ), which will bind to actin via the zonula occludens-1, -2 and -3 (ZO-1, ZO-2 and ZO-3) in SCs 9 . At stage VII-VIII of the epithelial cycle, the preleptotene and leptotene spermatocytes must move through the BTB and enter the adluminal compartment 10 .…”

Myosin VI maintains the actin-dependent organization of the tubulobulbar complexes required for endocytosis during mouse spermiogenesis†‡

“…At the late phase of spermiogenesis, the apical ES is replaced by highly specialized endocytic structure of membranes and actin filaments (AFs) called the apical TBC (Figure 1a and b). These unique complexes are formed at stage VII of the seminiferous epithelium cycle in mouse and have been suggested to play a role in the internalization and recycling of adhering junctions of the apical ES and thus are crucial for the sperm release during spermiation [2,3]. The TBC consists of fingerlike double-membraned invaginations of the Sertoli cell and the spermatid plasma membranes.…”