An isoform of Kalirin, a brain-specific GDP/GTP exchange factor, is enriched in the postsynaptic density fraction

Peter Penzes, Richard C. Johnson, M. Rashid Alam, Vikram Kambampati, Richard E. Mains, Betty A. Eipper*

*Corresponding author for this work

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

Communication between membranes and the actin cytoskeleton is an important aspect of neuronal function. Regulators of actin cytoskeletal dynamics include the Rho-like small GTP-binding proteins and their exchange factors. Kalirin is a brain-specific protein, first identified through its interaction with peptidylglycine-α-amidating monooxygenase. In this study, we cloned rat Kalirin-7, a 7-kilobase mRNA form of Kalirin. Kalirin-7 contains nine spectrin-like repeats, a Dbl homology domain, and a pleckstrin homology domain. We found that the majority of Kalirin-7 protein is associated with synaptosomal membranes, but a fraction is cytosolic. We also detected higher molecular weight Kalirin proteins. In rat cerebral cortex, Kalirin-7 is highly enriched in the postsynaptic density fraction. In primary cultures of neurons, Kalirin-7 is detected in spine-like structures, while other forms of Kalirin are visualized in the cell soma and throughout the neurites. Kalirin-7 and its Dbl homology-pleckstrin homology domain induce formation of lamellipodia and membrane ruffling, when transiently expressed fibroblasts, indicative of Rac1 activation. Using Rac1, the Dbl homology- pleckstrin homology domain catalyzed the in vitro exchange of bound GDP with GTP. Kalirin-7 is the first guanine-nucleotide exchange factor identified in the postsynaptic density, where it is positioned optimally to regulate signal transduction pathways connecting membrane proteins and the actin cytoskeleton.

Original languageEnglish (US)
Pages (from-to)6395-6403
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number9
DOIs
StatePublished - Mar 3 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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