Rin, a neuron-specific and calmodulin-binding small G-protein, and Rit define a novel subfamily of Ras proteins

Ching Hsien J. Lee, Neil G. Della, Christina E. Chew, Donald J. Zack

Research output: Contribution to journalArticlepeer-review

Abstract

cDNAs encoding two novel 25 kDa Ras-like proteins, Rit and Rin, were isolated from mouse retina using a degenerate PCR-based cloning strategy. Using the expressed sequence tag database, human orthologs were also obtained and sequenced. The protein sequences of Rit and Rin, which are 64% identical, are more similar to each other than to any known Ras protein. Their closest homologs in the databases are Mucor racemosus Ras2 and Ras3, to which they show ~48% identity. Rit and Rin both bind GTP in vitro. An unusual feature of their structure is that they lack a known recognition signal for C- terminal lipidation, a modification that is generally necessary for plasma membrane association among the Ras subfamily of proteins. Nonetheless, transiently expressed Rit and Rin are plasma membrane-localized. Both proteins contain a C-terminal cluster of basic amino acids, which could provide a mechanism for membrane association. Deletion analysis suggested that this region is important for Rit membrane binding but is not necessary for Rin. Rit, like most Ras-related proteins, is ubiquitously expressed. Rin, however, is unusual in that it is expressed only in neurons. In addition, Rin binds calmodulin through a C-terminal binding motif. These results suggest that Rit and Rin define a novel subfamily of Ras-related proteins, perhaps using a new mechanism of membrane association, and that Rin may be involved in calcium-mediated signaling within neurons.

Original languageEnglish (US)
Pages (from-to)6784-6794
Number of pages11
JournalJournal of Neuroscience
Volume16
Issue number21
DOIs
StatePublished - Nov 1 1996

Keywords

  • CAAX box
  • Ras-like protein
  • calcium signaling
  • calmodulin
  • neuron-specific
  • signal transduction
  • small G-protein

ASJC Scopus subject areas

  • Neuroscience(all)

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