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9.B.12 The Sensitivity to Sodium or Salt Stress-induced Hydrophobic Peptide (Sna) Family

The Sna family (also referred to as the SHP family or the UPF0057 family by UniProt) consists of peptides found ubiquitously in bacteria, yeast, plants and animals. There are four members of the SHP family encoded within the S. cerevisiae genome, at least eight in C. elegans and two in Synechocystis. Expression of the gene encoding one member of the SHP family, a peptide from barley or 'tall wheat grass' (L. elongatum), has been shown to be induced by both salt and low temperature stress.

Yeast (S. cerevisiae and Candida albicans) plasma membranes contain a non-essential 55 aa hydrophobic peptide (Pmp3p) with two putative TMSs and sequence similarity to a ubiquitous protein family. One plant peptide (LT16A or RC12A; gbAAF26091) is over-expressed under high salt or low temperature conditions. One C. elegans protein (pirT26079) is large (551 aas) with the region of sequence similarity at the C-terminus, while two others (pirS40492 and T16929) are small (92 aas and 77 aas) with the region of homology at the N-terminus and the C-terminus, respectively. The PMP3 gene product in yeast possibly gives rise to hyperpolarization of the membrane potential, promoting sensitivity to cytotoxic cations such as Na+ and hygromycin B. The plant homologue, RC12A, can replace Pmp3p. These results could be explained if Pmp3p forms oligomeric pores that conduct H+ or another cation.

The Plasma Membrane Proteolipid 3 (PMP3, UPF0057 family in Uniprot) family consists of abundant small hydrophobic polypeptides with two predicted transmembrane helices. Plant homologues are upregulated in response to drought/salt-stresses, and yeast deletion mutants exhibited conditional growth defects. Kwok et al. 2020 reported abundant expression of Group I PMP3 homologues (PMP3(i)hs) during normal vegetative growth in both prokaryotic and eukaryotic cells, at a level comparable to housekeeping genes. Expression of eukaryotic PMP3(i)hs is dramatically upregulated in response to membrane potential (Vm) variability (Vmvar ), whereas PMP3(i)hs deletion-knockdown led to Vm changes with conditional growth defects. Bacterial PMP3(i)h yqaE deletion led to a shift in salt sensitivity; Vmvar alternations with exogenous K+ addition downregulated prokaryotic PMP3(i)hs, suggesting that the [K+]-Vmvar axis involves a significant feedback element in prokaryotic ionic homeostasis. The eukaryotic homologues functionally suppressed the conditional growth defects in bacterial deletion mutants, demonstrating the conserved cross-kingdom membrane function. Thus, thee is a direct reciprocal relationship between PMP3(i)hs expression and Vm differentials in both prokaryotic and eukaryotic cells. Together with PMP3(i)hs ubiquitous abundance, Kwok et al. 2020 proposed that the lipid-binding selectivity and membrane protein colocalization is a key element in membrane homeostasis.

References associated with 9.B.12 family:

Goddard, N.J., M.A. Dunn, L. Zhang, A.J. White, P.L. Jack and M.A. Hughes (1993). Molecular analysis and spatial expression pattern of a low-temperature-specific barley gene, blt101. Plant Mol. Biol. 23: 871-879. 8251639
Gulick, P.J., W. Shen and H. An (1994). ESI3, a stress-induced gene from Lophopyrum elongatum. Plant Physiol. 104: 799-800. 8159795
Kwok, A.C.M., F. Zhang, Z. Ma, W.S. Chan, V.C. Yu, J.S.H. Tsang, and J.T.Y. Wong. (2020). Functional responses between PMP3 small membrane proteins and membrane potential. Environ Microbiol 22: 3066-3080. 32307863
Navarre, C. and A. Goffeau. (2000). Membrane hyperpolarization and salt sensitivity induced by deletion of PMP3, a highly conserved small protein of yeast plasma membrane. EMBO. J. 19: 2515-2524. 10835350
Pokrzywa, W., B. Guerriat, J. Dodzian, and P. Morsomme. (2009). Dual sorting of the Saccharomyces cerevisiae vacuolar protein Sna4p. Eukaryot. Cell. 8: 278-286. 19168755
Renard, H.F., D. Demaegd, B. Guerriat, and P. Morsomme. (2010). Efficient ER exit and vacuole targeting of yeast Sna2p require two tyrosine-based sorting motifs. Traffic 11: 931-946. 20406419
Stawiecka-Mirota, M., W. Pokrzywa, J. Morvan, T. Zoladek, R. Haguenauer-Tsapis, D. Urban-Grimal, and P. Morsomme. (2007). Targeting of Sna3p to the endosomal pathway depends on its interaction with Rsp5p and multivesicular body sorting on its ubiquitylation. Traffic 8: 1280-1296. 17645729