Identification and characterization of two mature isoforms of retinoschisin in murine retina

Camasamudram Vijayasarathy, Mary Ann Gawinowicz, Yong Zeng, Yuichiro Takada, Ronald A. Bush, Paul A. Sieving

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Retinoschisin (RS) is a 24 kDa secreted protein expressed in retina and is required for the structural and functional integrity of the retina. RS has been predicted to serve as an adhesive protein but the precise molecular mechanism by which it functions in retina is not yet known. During investigations on structural and functional aspects of RS in murine retina using proteomic tools, we identified two isoforms of RS that differed in mass by 200 Da with no apparent change in charge. Mass spectra and amino acid sequence analysis of the tryptic peptides revealed that these isoforms differed by two amino acids at the N-terminus which suggested processing of RS signal sequence at two cleavage sites by signal peptidase as the basic mechanism underlying the occurrence of two mature RS isoforms in retina. Bioinformatic analysis identified two potential cleavage sites (between amino acids 21-22 and 23-24) in RS signal sequence. The flexibility of the signal peptidase to cleave at two sites is correlated to the amino acid composition of the RS signal sequence. This finding represents a rare example of a naturally occurring signal sequence cleavage at more than one site in vivo.

Original languageEnglish (US)
Pages (from-to)99-105
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume349
Issue number1
DOIs
StatePublished - Oct 13 2006
Externally publishedYes

Keywords

  • Isoforms
  • Missense mutations
  • Post-translational Modifications
  • Processing
  • Retina
  • Retinoschisin
  • Signal peptidase
  • Signal Sequence
  • X-linked retinoschisis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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