title: Pur-alpha regulates RhoA developmental expression and downstream signaling.
abstract: Pur-alpha is an essential protein for postnatal brain development which localizes specifically to dendrites where it plays a role in the translation of neuronal RNA. Mice lacking Pur-alpha display decreased neuronogenesis and impaired neuronal differentiation. Here we examined two Rho GTPases, Rac1 and RhoA, which play opposing roles in neurite outgrowth and are critical for dendritic maturation during mouse brain development in the presence and absence of Pur-alpha. Pur-alpha is developmentally regulated in the mouse brain with expression beginning shortly after birth and rapidly increasing to peak during the third week of postnatal development. RhoA levels analyzed by Western blotting rapidly fluctuated in the wild-type mouse brain, however, in the absence of Pur-alpha, a decrease in RhoA levels shortly after birth and a delay in the cycling of RhoA regulation was observed leading to reduced basal levels of RhoA after day 10 postnatal. Immunohistochemistry of brain tissues displayed reduced RhoA levels in the cortex and cerebellum and loss of perinuclear cytoplasmic labeling of RhoA within the cortex in the knockout mouse brain. While Rac1 levels remained relatively stable at all time points during development and were similar in both wild-type and Pur-alpha knockout mice, changes in subcellular localization of Rac1 were seen in the absence of Pur-alpha. These findings suggest that Pur-alpha can regulate RhoA at multiple levels including basal protein levels, subcellular compartmentalization, as well as turnover of active RhoA in order to promote dendritic maturation.
authors.affiliation: Department of Neuroscience and Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Mamata
authors.initials: M
authors.lastname: Mishra
authors.forename: Luis
authors.initials: L
authors.lastname: Del Valle
authors.forename: Jessica
authors.initials: J
authors.lastname: Otte
authors.forename: Nune
authors.initials: N
authors.lastname: Darbinian
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gordon
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000906:Antibodies; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C501130:PURA protein, human; C121485:Pura protein, mouse; D014157:Transcription Factors; D020742:rhoA GTP-Binding Protein