Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes.
Proc Natl Acad Sci U S A
; 106(31): 13058-63, 2009 Aug 04.
Article
in En
| MEDLINE
| ID: mdl-19625617
ABSTRACT
Dendritic spine morphogenesis contributes to brain function, cognition, and behavior, and is altered in psychiatric disorders. Kalirin is a brain-specific guanine-nucleotide exchange factor (GEF) for Rac-like GTPases and is a key regulator of spine morphogenesis. Here, we show that KALRN-knockout mice have specific reductions in cortical, but not hippocampal, Rac1 signaling and spine density, and exhibit reduced cortical glutamatergic transmission. These mice exhibit robust deficits in working memory, sociability, and prepulse inhibition, paralleled by locomotor hyperactivity reversible by clozapine in a kalirin-dependent manner. Several of these deficits are delayed and age-dependent. Our study thus links spine morphogenic signaling with age-dependent, delayed, disease-related phenotypes, including cognitive dysfunction.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Guanine Nucleotide Exchange Factors
/
Dendritic Spines
/
Frontal Lobe
Limits:
Animals
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2009
Document type:
Article
Affiliation country:
United States