The Role of ITM2B and Associated Proteins in Sperm Capacitation and Aging

Integral membrane protein 2 (F1RK12, upregulated protein), encoded by ITM2B, has been found to be associated with ADAM2, promoting sperm capacitation, as reported by Han C et al. The function of I3LH92 protein, encoded by AQP2, may be related to maintaining a suitable luminal environment for sperm maturation. KCMF1 (A0A5G2Q6P4), a novel component of the ubiquitin ligase complex BICR6, exhibits inherent E3 ubiquitin ligase activity and facilitates ubiquitination in response to comprehensive stress. QPCT (F1S4Q8) is a modifying enzyme of CD47, both of which are highly expressed in senescent cells. AP2S1 (I3LG98) participates in calcium-regulated signaling pathways, while ATP5MK (F1RFD4) regulates ATP synthesis within mitochondria. Calcium channels and ATP synthesis are known to be essential for sperm capacitation. Calcium influx through the plasma membrane and intracellular stores triggers a cascade of events leading to capacitation, including protein phosphorylation, hyperactivation, and the acrosomal reaction. During the capacitation process, sperm undergoes metabolic alterations that enhance both ATP production and consumption. Finkelstein M, Darszon A et al. have investigated the roles of specific calcium channels, transporters, and regulatory proteins in sperm capacitation, and Yang Q et al. have also highlighted the involvement of ATP metabolism and calcium ion channels in the process of sperm capacitation. Based on protein quantification results, most proteins interacting with ITM2B were found to be upregulated in the PRE group of sperm, including I3LH92, A0A5G2Q6P4, F1S4Q8, I3LG98, and F1RFD4. Therefore, it is speculated that these proteins interact with ITM2B to regulate the processes of sperm capacitation and the acrosomal reaction, accelerating sperm energy consumption and senescence.