title: An isoform of kalirin, a brain-specific GDP/GTP exchange factor, is enriched in the postsynaptic density fraction.
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-alpha-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 in 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.
authors.affiliation: Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: P
authors.initials: P
authors.lastname: Penzes
authors.forename: R C
authors.initials: RC
authors.lastname: Johnson
authors.forename: M R
authors.initials: MR
authors.lastname: Alam
authors.forename: V
authors.initials: V
authors.lastname: Kambampati
authors.forename: R E
authors.initials: RE
authors.lastname: Mains
authors.forename: B A
authors.initials: BA
authors.lastname: Eipper
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins; D002458:Cell Fractionation; D002478:Cells, Cultured; D003599:Cytoskeleton; D005455:Fluorescent Antibody Technique; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D013574:Synaptosomes / Q000737:chemistry; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; C102365:Kalrn protein, rat; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D020830:rac1 GTP-Binding Protein