title: BAG3 is involved in neuronal differentiation and migration.
abstract: Bcl2-associated athanogene 3 (BAG3) protein belongs to the family of co-chaperones interacting with several heat shock proteins. It plays a key role in protein quality control and mediates the clearance of misfolded proteins. Little is known about the expression and cellular localization of BAG3 during nervous system development and differentiation. Therefore, we analyze the subcellular distribution and expression of BAG3 in nerve-growth-factor-induced neurite outgrowth in PC12 cells and in developing and adult cortex of mouse brain. In differentiated PC12 cells, BAG3 was localized mainly in the neuritic domain rather than the cell body, whereas in control cells, it appeared to be confined to the cytoplasm near the nuclear membrane. Interestingly, the change of BAG3 localization during neuronal differentiation was associated only with a slight increase in total BAG3 expression. These data were coroborated by transmission electron microscopy showing that BAG3 was confined mainly within large dense-core vesicles of the axon in differentiated PC12 cells. In mouse developing cortex, BAG3 appeared to be intensely expressed in cellular processes of migrating cells, whereas in adult brain, a diffuse expression of low to medium intensity was detected in neuronal cell bodies. These findings suggest that BAG3 expression is required for neuronal differentiation and migration and that its role is linked to a change in its distribution pattern rather than to an increase in its protein expression levels.
authors.affiliation: Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana", University of Salerno, Salerno, Italy. ansantoro@unisa.it.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Santoro
authors.affiliation: Clinical Department of Medical, Surgical and Health Science, University of Trieste, Trieste, Italy.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Nicolin
authors.affiliation: Confocal microscopy unit, National Research Council, European Brain Research Institute (EBRI), Rome, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Florenzano
authors.affiliation: Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana", University of Salerno, Salerno, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rosati
authors.affiliation: Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana", University of Salerno, Salerno, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Capunzo
authors.affiliation: Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana", University of Salerno, Salerno, Italy. snori@unisa.it.
authors.forename: Stefania L
authors.initials: SL
authors.lastname: Nori
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C498807:BAG3 protein, rat; C498806:Bag3 protein, mouse
keywords: BAG3; Large dense-core vesicles; Mouse cerebral cortex; Neuronal differentiation; PC12 cells