Acrosome biogenesis: Revisiting old questions to yield new insights

Abstract

The acrosome is a unique membranous organelle located over the anterior part of the sperm nucleus that is highly conserved throughout evolution. This acidic vacuole contains a number of hydrolytic enzymes that, when secreted, help the sperm penetrate the egg's coats. Although acrosome biogenesis is an important aspect of spermiogenesis, the molecular mechanism(s) that regulates this event remains unknown. Active trafficking from the Golgi apparatus is involved in acrosome formation, but experimental evidence indicates that trafficking of vesicles out of the Golgi also occurs during acrosomogenesis. Unfortunately, this second aspect of acrosome biogenesis remains poorly studied. In this article, we briefly discuss how the biosynthetic and endocytic pathways, assisted by a network of microtubules, tethering factors, motor proteins and small GTPases, relate and connect to give rise to the sperm-specific vacuole, with a particular emphasis placed on the endosomal compartment. It is hoped that this information will be useful to engage more studies on acrosome biogenesis by focusing attention towards suggested directions.

Figure 1

Schematic representation of the biogenesis of the acrosome proposed as a LRO. Golgi-derived biosynthetic cargo destined for the acrosome is sorted at level of the TGN. Here some protein cargo is packed directly or by the way of the EE (green dashed arrows) in the electron-dense pro-acrosomal granule (PG), while some membrane cargo is sorted to the plasma membrane (green dashed arrow). This membrane cargo is then recruited, through the cross-talk endocytic regulators/polarity proteins, to the EE and hereinafter is destined (yellow arrows) to the correct membrane domain of the developing pro-acrosome (PA). The same fate characterises further protein cargo that once marked with the ubiquitin signature (red coat) at the plasma membrane is selectively recognized by the UBPy/ESCRT-0 complex and recruited to the EE (yellow arrow). The endocytosed vesicular protein/membrane cargoes destined to the acrosome (yellow arrows) are tethered by Vps54 from the EE to the PA, which not only grows, but flattens and acquires its characteristic shape to develop into the acrosome (A). Some EE protein content is, however, destined to the multivesicular body (MVB) that, not evolving into a lysosome, is hypothesized to be discarded into the cytoplasmic body.