Alternative splicing and genomic organization of the SLAP gene encoding sarcolemmal-associated proteins.
|Title:||Alternative splicing and genomic organization of the SLAP gene encoding sarcolemmal-associated proteins.|
|Authors:||Wielowieyski, Paul A.|
|Abstract:||Sarcolemmal-associated proteins (SLAPs) are a family of acidic amphipathic alpha-helical proteins associated with the membrane. Different size SLAP transcripts were identified and shown to encode polypeptides of 37, 46 and 74 kDa designated by SLAP1, SLAP2 and SLAP3, respectively. The SLAP1 and SLAP2 transcripts were expressed in cardiac, soleus and smooth muscle, whereas SLAP3 was expressed ubiquitously. The subcellular distribution studies localized SLAPs to cell membrane, as well as sarco/endoplasmic reticulum membrane and transverse-tubules. The SLAP family is encoded by a single gene which was mapped to a human chromosome 3p14.3-21.2 and the various transcripts are perhaps generated by alternative promoter and/or alternative splicing. In order to understand the molecular basis underlying the SLAP isoform diversity studies were carried out to elucidate the genomic organization of the SLAP gene. The 3$\sp\prime$ end of SLAP gene is composed of 11 exons spanning over 35 kb, that range in size from 60 to 321 bp. SLAP introns on the other hand, range in size from 0.2 to 5.5 kb and all conform to a canonical GT-AG rule. Results suggest that SLAP primary transcript is alternatively spliced and that the expression of alternative variants is regulated in a developmental and tissue specific manner. Moreover, RT-PCR and cDNA library screening isolated alternatively spliced human, rabbit and rat orthologues that have been evolutionarily conserved which is indicative of a functional role of the various variants. Although the function of various SLAP variants remains unknown the alternative splicing is predicted to introduce putative phosphorylation sites, influence secondary structure and perhaps alter subcellular localization. In summary, heterogeneity due to alternative usage of the N-terminal of SLAP combined with the diversity generated by alternative splicing is predicted to give rise to 36 distinct SLAP isoforms, that may perhaps play distinct roles in the membrane function.|
|Collection||Thèses, 1910 - 2010 // Theses, 1910 - 2010|