Bral2 is indispensable for the proper localization of brevican and the structural integrity of the perineuronal net in the brainstem and cerebellum

Yoko Bekku, Mai Saito, Markus Moser, Maki Fuchigami, Ami Maehara, Masaru Nakayama, Shozo Kusachi, Yoshifumi Ninomiya, Toshitaka Oohashi

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1721-1736
Number of pages16
JournalJournal of Comparative Neurology
Volume520
Issue number8
DOIs
Publication statusPublished - Jun 1 2012

Fingerprint

Brevican
Neurocan
Cerebellum
Brain Stem
Aggrecans
Central Nervous System
Chondroitin Sulfate Proteoglycans
Neurons
Cerebellar Nuclei
Visual Cortex
Dendrites
Glycosaminoglycans
Synapses
Extracellular Matrix
link protein

Keywords

  • Extracellular matrix
  • Link protein
  • Perineuronal net
  • Proteoglycan

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Bral2 is indispensable for the proper localization of brevican and the structural integrity of the perineuronal net in the brainstem and cerebellum. / Bekku, Yoko; Saito, Mai; Moser, Markus; Fuchigami, Maki; Maehara, Ami; Nakayama, Masaru; Kusachi, Shozo; Ninomiya, Yoshifumi; Oohashi, Toshitaka.

In: Journal of Comparative Neurology, Vol. 520, No. 8, 01.06.2012, p. 1721-1736.

Research output: Contribution to journalArticle

Bekku, Yoko ; Saito, Mai ; Moser, Markus ; Fuchigami, Maki ; Maehara, Ami ; Nakayama, Masaru ; Kusachi, Shozo ; Ninomiya, Yoshifumi ; Oohashi, Toshitaka. / Bral2 is indispensable for the proper localization of brevican and the structural integrity of the perineuronal net in the brainstem and cerebellum. In: Journal of Comparative Neurology. 2012 ; Vol. 520, No. 8. pp. 1721-1736.
@article{4b694c4c3065465cbacee9cabc166ad3,
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.",
keywords = "Extracellular matrix, Link protein, Perineuronal net, Proteoglycan",
author = "Yoko Bekku and Mai Saito and Markus Moser and Maki Fuchigami and Ami Maehara and Masaru Nakayama and Shozo Kusachi and Yoshifumi Ninomiya and Toshitaka Oohashi",
year = "2012",
month = "6",
day = "1",
doi = "10.1002/cne.23009",
language = "English",
volume = "520",
pages = "1721--1736",
journal = "Journal of Comparative Neurology",
issn = "0021-9967",
publisher = "Wiley-Liss Inc.",
number = "8",

}

TY - JOUR

T1 - Bral2 is indispensable for the proper localization of brevican and the structural integrity of the perineuronal net in the brainstem and cerebellum

AU - Bekku, Yoko

AU - Saito, Mai

AU - Moser, Markus

AU - Fuchigami, Maki

AU - Maehara, Ami

AU - Nakayama, Masaru

AU - Kusachi, Shozo

AU - Ninomiya, Yoshifumi

AU - Oohashi, Toshitaka

PY - 2012/6/1

Y1 - 2012/6/1

N2 - 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.

AB - 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.

KW - Extracellular matrix

KW - Link protein

KW - Perineuronal net

KW - Proteoglycan

UR - http://www.scopus.com/inward/record.url?scp=84859322500&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859322500&partnerID=8YFLogxK

U2 - 10.1002/cne.23009

DO - 10.1002/cne.23009

M3 - Article

VL - 520

SP - 1721

EP - 1736

JO - Journal of Comparative Neurology

JF - Journal of Comparative Neurology

SN - 0021-9967

IS - 8

ER -