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8.A.36 The Trp-3 (SPE-41) Interaction Protein (SPE-38) Family

Despite undergoing normal development and acquiring normal morphology and motility, mutations in spe-38 or trp-3/spe-41 cause identical phenotypes in Caenorhabditis elegans mutant sperm. These mutants fail to fertilize oocytes despite direct contact. SPE-38 is a four-pass transmembrane protein, and TRP-3/SPE-41 is a Ca2+-permeable channel (1.A.4.1.6). Localization of both of these proteins is confined to the membranous organelles (MOs) in undifferentiated spermatids. In mature spermatozoa, SPE-38 is localized to the pseudopod and TRP-3/SPE-41 is localized to the whole plasma membrane. Singaravelu et al. (2012) showed that the dynamic redistribution of TRP-3/SPE-41 from MOs to the plasma membrane is dependent on SPE-38. In spe-38 mutant spermatozoa, TRP-3/SPE-41 is trapped within the MOs and fails to reach the cell surface despite MO fusion with the plasma membrane. The cell surface localization of TRP-3/SPE-41 is regulated by SPE-38 through a direct protein-protein interaction mechanism. Sequences that influence the physical interaction between SPE-38 and TRP-3/SPE-41 have been identified, and these sequences in SPE-38 are required for fertility in transgenic animals. Despite the mislocalization of TRP-3/SPE-41 in spe-38 mutant spermatozoa, ionomycin or thapsigargin induced influx of Ca2+ remained unperturbed. This work revealed a new paradigm for the regulated surface localization of a Ca2+-permeable channel (Singaravelu et al., 2012).

Blast searches reveal that Spe-38 is distantly related to 4 TMS proteins from species of Campylobacter (8.A.36.2.1) and other bacteria. These proteins belong to the Etoposide-induced protein 2.4 (EI24) superfamily which is represented in both prokaryote and eukaryotes.  Some eukaryotes are ~350aas long; bacterial Cys7 proteins (TC#9.B.7 Duf540) are also members.

References associated with 8.A.36 family:

Singaravelu, G., I. Chatterjee, S. Rahimi, M.K. Druzhinina, L. Kang, X.Z. Xu, and A. Singson. (2012). The sperm surface localization of the TRP-3/SPE-41 Ca2+ -permeable channel depends on SPE-38 function in Caenorhabditis elegans. Dev Biol 365: 376-383. 22425620