title: Bral2 is indispensable for the proper localization of brevican and the structural integrity of the perineuronal net in the brainstem and cerebellum.
abstract: Perineuronal nets (PNNs) are pericellular coats of condensed matrix that enwrap the cell bodies and dendrites of many adult central nervous system (CNS) neurons. These extracellular matrices (ECMs) play a structural role as well as instructive roles in the control of CNS plasticity and the termination of critical periods. The cartilage link protein Crtl1/Hapln1 was reported to be a trigger for the formation of PNNs in the visual cortex. Bral2/Hapln4 is another link protein that is expressed in PNNs, mainly in the brainstem and cerebellum. To assess the role of Bral2 in PNN formation, we examined the expression of PNN components in targeted mouse mutants lacking Bral2. We show here that Bral2-deficient mice have attenuated PNNs, but the overall levels of chondroitin sulfate proteoglycans, lecticans, are unchanged with the exception of neurocan. Bral2 deficiency markedly affected the localization of brevican in all of the nuclei tested, and neurocan concomitant with Crtl1 in some of the nuclei, whereas no effect was seen on aggrecan even with the attenuation of Crtl1. Bral2 may have a role in the organization of the PNN, in association with brevican, that is independent of aggrecan binding. There was a heterogenous attenuation of PNN components, including glycosaminoglycans, indicating the elaborate molecular organization of the PNN components. Strikingly, a slight decrease in the number of synapses in deep cerebellar nuclei neurons was found. Taken together, these results imply that Bral2-brevican interaction may play a key role in synaptic stabilization and the structural integrity of the PNN.
authors: Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors: Yoko
authors: Y
authors: Bekku
authors: Mai
authors: M
authors: Saito
authors: Markus
authors: M
authors: Moser
authors: Maki
authors: M
authors: Fuchigami
authors: Ami
authors: A
authors: Maehara
authors: Masaru
authors: M
authors: Nakayama
authors: Shozo
authors: S
authors: Kusachi
authors: Yoshifumi
authors: Y
authors: Ninomiya
authors: Toshitaka
authors: T
authors: Oohashi
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D001933:Brain Stem / Q000378:metabolism*; D058581:Brevican / Q000378:metabolism*; D002531:Cerebellum / Q000737:chemistry / Q000378:metabolism*; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000737:chemistry / Q000378:metabolism; D000099249:Proteoglycan Link Protein
chemical_list: D058581:Brevican; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; C480570:Hapln4 protein, mouse; D000099249:Proteoglycan Link Protein