Identification and characterization of splicing variants of PLEKHA5 (Plekha5) during brain development

Gene. 2012 Jan 15;492(1):270-5. doi: 10.1016/j.gene.2011.10.018. Epub 2011 Oct 20.

Abstract

PLEKHA5 (pleckstrin homology domain-containing protein family A, member 5) belongs to the PLEKHA family (PLEKHA1-6); however, the properties of this protein remain poorly characterized. We have identified and characterized two forms of PLEKHA5 mRNA. The long form of PLEKHA5 (L-PLEKHA5) contains 32 exons, encodes 1282 amino acids, and is specifically expressed in the brain; the short form of PLEKHA5 (S-PLEKHA5) is generated by alternative splicing of L-PLEKHA5, contains 26 exons, encodes 1116 amino acids, and is ubiquitously expressed. Both forms of the protein contain putative Trp-Trp (WW) and pleckstrin homology (PH) domains and are located mainly in the cytosol. Developmental and age-dependent expression studies in the mouse brain have shown that Plekha5 is the most abundantly expressed protein at E13.5 with S-Plekha5 dominancy. L-Plekha5 levels increased gradually with the decrease in total Plekha5 levels; moreover, L-Plekha5 became the dominant protein at E17.5, maintaining its dominance throughout adulthood. Protein-lipid overlay assays have indicated that the PH domain of PLEKHA5 specifically interacts with PI3P, PI4P, PI5P, and PI(3,5)P2. These results suggest that the S- to L-conversion of PLEKHA5 (Plekha5) may play an important role in brain development through association with specific phosphoinositides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Brain / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Gene Expression Regulation
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Mice
  • Protein Isoforms / genetics*
  • Transfection

Substances

  • Intracellular Signaling Peptides and Proteins
  • PLEKHA5 protein, human
  • Plekha5 protein, mouse
  • Protein Isoforms