80K H protein Several selleck chemicals studies suggest that store operated calcium channels in mammalian sperm belong to the transient receptor potential family of cation channels, whose members are closely related to the TRP gene expressed in Drosophilia photoreceptors. Five mem bers of the TRP channel family have been detected in mammalian sperm, of which 4 localize Inhibitors,Modulators,Libraries to the head of the human sperm. More important, maito toxin, which induces Ca2 uptake through its action on TRP channels, is the most potent inducer of the acro some reaction in mouse sperm aside from ZP. TRPC2 has been proposed to participate in the sus tained Ca2 influx triggered by ZP3 in mouse sperm, although it appears to be a pseudogene in humans.
TRPC channels can form heteromultimers, and it is likely that the store operated Ca2 entry path way in sperm involves several family members, which can at least partly substitute for each others, as TRPC2 null mice are fertile. Several TRP channel regulating Inhibitors,Modulators,Libraries molecules have been identified, including STIM, junctate, PIP2, enkurin, and 80K H. While enkurin and junc tate previously have been detected in mouse sperm, this is the first demonstration of the 80K H pro tein in a mammalian sperm. 80K H is a multifunctional Ca2 sensor originally identified as a substrate for PKC. 80K H has been associated with the regulation of intracellular signaling downstream of both the fibroblast growth factor recep tor and the advanced glycosylation end products receptor, and it participates in the regulation of protein translocation. 80K H interacts with PKC and munc18c to induce glucose transporter 4 transloca tion to the plasma membrane.
A recent study sug gests that 80K H can regulate IP3 induced calcium release by interacting with the cytoplasmic tail of IP3 receptors. Finally, 80K H has been shown to inter act with and regulate the activity of the epithelial TRP channel V5. The plasma membrane den sity and activity of TRPV5 channels appear to be regu lated via changes in their extracellular glycosylation status. Inhibitors,Modulators,Libraries Processing of specific N linked carbohydrate sidechains from the ectodomain of TRPV5 channels is Inhibitors,Modulators,Libraries thought to entrap them in the plasma membrane, result ing in increased Ca2 influx. This is noteworthy, as 80K H acts as the regulatory subunit of a glucosidase II, an N linked glycan processing enzyme. Several studies have indicated a major role for PKC in the upregulation of cytosolic calcium levels prior to the AR in human sperm, and Inhibitors,Modulators,Libraries it has been suggested that PKC participates selleck chemicals llc in the opening of store operated calcium channels in the sperm plasma membrane. However the molecular mechanism by which PKC controls capacitative calcium entry has remained elusive.
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