mUBPY, endocytic vesicle traffic and microtubule mediated transport in acrosome biogenesis. Comparative study between wild-type and Wobbler (L967Q Vps54) mice

Acrosome biogenesis is a multistep process, essential for fertilization, involving poorly understood events, like vesicular trafficking and microtubular transport. We found that the deubiquitinating enzyme UBPy, in mouse, marks step-by-step the development of the acrosomal vesicle. Recently by studies on transfected cells, UBPy is emerging to play a key and no redundant role in endosomal sorting, resulting to be fundamental for the cell life. In this work we studied in male germ cells the endosomal trafficking machinery, in particular we detected the early endosome compartment and the ESCRT-0 complex, interestingly mUBPy colocalizes and interacts with Hrs and Hbp (Hrs-binding protein) at the early endosomes. We investigated also Vps54, a component of the Golgi associated retrograde protein complex which is involved in vesicles transport from early endosomes to trans Golgi network. Altogether our findings demonstred for the first time the presence of a mutiprotein complex in spermatogenic cells. Interestingly, proteins belonging to vesicular compartment participate and cooperate with UBPy to the formation of the acrosome, and here remain in the mature sperm, strongly suggesting that the endosome system, through an UBPy-microtubular manchette-mediated transport, could contribute to the biogenesis of the acrosome. The missense mutation L967Q in Vps54 marks the wobbler mouse phenotype. Wobbler mouse is an animal model for motor neuron neurodegenerative disorders with associated male sterility. We provided the first characterization of wobbler reproductive apparatus, detecting the absence of the acrosome, an abnormal shape of sperm s head and a defective vesicular transport.