Multiple isoforms of the tumor protein p73 are expressed in the adult human telencephalon and choroid plexus and present in the cerebrospinal fluid.
p73, a homolog of the p53 tumor suppressor, codes for full-length transactivating (TA) and N-terminally truncated (DeltaN) isoforms, with pro- and anti-apoptotic activities, respectively. We examined the expression of the main p73 isoforms in adult human and mouse telencephalon and choroid plexus by immunohistochemistry on paraffin sections, and immunoblotting (IB) of tissue extracts and cerebrospinal fluid (CSF), using antibodies against different protein domains. Cortical neurons expressed TAp73 predominantly in the cytoplasm and DeltaNp73 mainly in the nucleus, with partial overlap in the cytoplasm. Highest expression was found in the hippocampus. IB showed an array of TAp73 variants in adult human cortex and hippocampus. IB of human choroid plexus and CSF using TAp73-specific antibodies revealed the presence of a approximately 90-kDa protein whose molecular weight was reduced after N-deglycosylation, suggesting that glycosylated TAp73 is exported into the CSF. In the mouse, high expression of TAp73 was also detected in the subcommissural organ (SCO), an ependymal gland absent in adult humans. TAp73 colocalized with anti-fibra-Reissner-antibody (AFRU), which is a marker of Reissner's fiber, the secreted SCO product. p73-deficient mice had generalized cortical hypoplasia and hydrocephalus; in addition, we observed a dramatic size reduction of the choroid plexus. However, the SCOs were apparently unaltered and continued to secrete Reissner's fiber. Our findings point to complex and widespread p73 activities in the maintenance of adult cortical neurons and in brain homeostasis. TAp73 in the CSF may play important roles in the maintenance of the adult ventricular wall as well as in the development of the proliferating neuroepithelium.
Cabrera-Socorro
Alfredo
A
Department of Anatomy, Faculty of Medicine, University of La Laguna, 38071, La Laguna, Spain.
Pueyo Morlans
Mercedes
M
Suarez Sola
Maria Luisa
ML
Gonzalez Delgado
Francisco J
FJ
Castañeyra-Perdomo
Agustin
A
Marin
Maria C
MC
Meyer
Gundela
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002460:Cell Line; D002831:Choroid Plexus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D008970:Molecular Weight; D016296:Mutagenesis / Q000502:physiology; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D013687:Telencephalon / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D015816:Cell Adhesion Molecules, Neuronal; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C108402:SCO-spondin; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human