title: PAK1 protein expression in the auditory cortex of schizophrenia subjects.
abstract: Deficits in auditory processing are among the best documented endophenotypes in schizophrenia, possibly due to loss of excitatory synaptic connections. Dendritic spines, the principal post-synaptic target of excitatory projections, are reduced in schizophrenia. p21-activated kinase 1 (PAK1) regulates both the actin cytoskeleton and dendritic spine density, and is a downstream effector of both kalirin and CDC42, both of which have altered expression in schizophrenia. This study sought to determine if there is decreased auditory cortex PAK1 protein expression in schizophrenia through the use of quantitative western blots of 25 schizophrenia subjects and matched controls. There was no significant change in PAK1 level detected in the schizophrenia subjects in our cohort. PAK1 protein levels within subject pairs correlated positively with prior measures of total kalirin protein in the same pairs. PAK1 level also correlated with levels of a marker of dendritic spines, spinophilin. These latter two findings suggest that the lack of change in PAK1 level in schizophrenia is not due to limited sensitivity of our assay to detect meaningful differences in PAK1 protein expression. Future studies are needed to evaluate whether alterations in PAK1 phosphorylation states, or alterations in protein expression of other members of the PAK family, are present in schizophrenia.
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Deo
authors.forename: Isaac M
authors.initials: IM
authors.lastname: Goldszer
authors.forename: Siyu
authors.initials: S
authors.lastname: Li
authors.forename: James V
authors.initials: JV
authors.lastname: DiBitetto
authors.forename: Ruth
authors.initials: R
authors.lastname: Henteleff
authors.forename: Allan
authors.initials: A
authors.lastname: Sampson
authors.forename: David A
authors.initials: DA
authors.lastname: Lewis
authors.forename: Peter
authors.initials: P
authors.lastname: Penzes
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sweet
mesh_terms: D000818:Animals; D001303:Auditory Cortex / Q000378:metabolism*; D016022:Case-Control Studies; D015971:Gene Expression Regulation, Enzymologic; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012559:Schizophrenia / Q000201:enzymology* / Q000378:metabolism; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C503866:KALRN protein, human; C515903:PAK1 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases