Identification and characterization of splicing variants of PLEKHA5 (Plekha5) during brain development.
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.
Department of Genetics, Institute for Developmental Research, Aichi Human Service Center, Aichi, Japan.
Kenichiro
K
Yamada
Noriko
N
Nomura
Arisa
A
Yamano
Yasukazu
Y
Yamada
Nobuaki
N
Wakamatsu
D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D020033:Protein Isoforms / Q000235:genetics*; D014162:Transfection
D047908:Intracellular Signaling Peptides and Proteins; C570565:PLEKHA5 protein, human; C570566:Plekha5 protein, mouse; D020033:Protein Isoforms