Figure 2.

Schematic of vesicle-dependent mechanisms that contribute to the creation of the highly specialized epididymal intraluminal milieu. Principal cells represents the dominant cell type throughout the length of the epididymis and are particularly active in terms of protein biosynthesis and secretion. At least two active secretory pathways have been documented in these cells, namely classical merocrine secretion and an alternative apocrine secretory pathway. The former is characterized by secretory vesicles formed by the Golgi apparatus and leads to the release of a myriad of soluble proteins. In contrast, apocrine secretion provides a pathway for the secretion of glycosyl-phosphatidylinositol-linked proteins and other hydrophobic proteins. These proteins generally require posttranslational modification in the Golgi apparatus, prior to being selectively packaged into exosome-like vesicles referred to as epididymosomes. These small vesicles are sequestered into large bleb-like structures protruding from the apical margin of the epithelial cells. The attachment anchoring the blebs to their parent cell progressively narrows to form a stalk-like process (potentially through reorganization of cytoskeletal proteins such as myosin and β-actin) and eventually undergoes scission leading to their shedding into the lumen and eventual degradation. The epididymosomes so released provide a mechanism for intercellular communication, thereby enabling the delivery of a complex macromolecular payload to recipient cells in the form of luminal spermatozoa and/or downstream epithelial cells. Such cargo are known to include several hundred proteins as well as various species of small non-protein coding RNA (sncRNA). At present, the mechanisms by which epididymosomes are tethered, and deliver their cargo, to recipient cells remains to be equivocally determined although various proteins have been implicated in this process. Principal cells may also participate in endocytosis, involving the uptake of epididymal luminal contents via receptor (e.g., LRP2) mediated mechanism(s). A similar function has also been assigned to the clear cell population, which is mainly responsible for the recycling of luminal components.