Coordinated internodal and paranodal adhesion controls accurate myelination by oligodendrocytes

Oligodendrocyte-axon contact is mediated by several cell adhesion molecules (CAMs) that are positioned at distinct sites along the myelin unit, yet their role during myelination remains unclear. Cadm4 and its axonal receptors, Cadm2 and Cadm3, as well as myelin-associated glycoprotein (MAG), are enr...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of cell biology Vol. 218; no. 9; p. 2887
Main Authors: Elazar, Nimrod, Vainshtein, Anya, Rechav, Katya, Tsoory, Michael, Eshed-Eisenbach, Yael, Peles, Elior
Format: Journal Article
Language:English
Published: United States 02.09.2019
Subjects:
Animals
Axons - metabolism
Cell Adhesion - genetics
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Cell Adhesion Molecules, Neuronal - genetics
Cell Adhesion Molecules, Neuronal - metabolism
Intercellular Junctions - genetics
Intercellular Junctions - metabolism
Mice
Mice, Knockout
Myelin Sheath - genetics
Myelin Sheath - metabolism
Myelin-Associated Glycoprotein - genetics
Myelin-Associated Glycoprotein - metabolism
Oligodendroglia - cytology
Oligodendroglia - metabolism
ISSN:1540-8140, 1540-8140
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Abstract Oligodendrocyte-axon contact is mediated by several cell adhesion molecules (CAMs) that are positioned at distinct sites along the myelin unit, yet their role during myelination remains unclear. Cadm4 and its axonal receptors, Cadm2 and Cadm3, as well as myelin-associated glycoprotein (MAG), are enriched at the internodes below the compact myelin, whereas NF155, which binds the axonal Caspr/contactin complex, is located at the paranodal junction that is formed between the axon and the terminal loops of the myelin sheath. Here we report that Cadm4-, MAG-, and Caspr-mediated adhesion cooperate during myelin membrane ensheathment. Genetic deletion of either Cadm4 and MAG or Cadm4 and Caspr resulted in the formation of multimyelinated axons due to overgrowth of the myelin away from the axon and the forming paranodal junction. Consequently, these mice displayed paranodal loops either above or underneath compact myelin. Our results demonstrate that accurate placement of the myelin sheath by oligodendrocytes requires the coordinated action of internodal and paranodal CAMs.
AbstractList Oligodendrocyte-axon contact is mediated by several cell adhesion molecules (CAMs) that are positioned at distinct sites along the myelin unit, yet their role during myelination remains unclear. Cadm4 and its axonal receptors, Cadm2 and Cadm3, as well as myelin-associated glycoprotein (MAG), are enriched at the internodes below the compact myelin, whereas NF155, which binds the axonal Caspr/contactin complex, is located at the paranodal junction that is formed between the axon and the terminal loops of the myelin sheath. Here we report that Cadm4-, MAG-, and Caspr-mediated adhesion cooperate during myelin membrane ensheathment. Genetic deletion of either Cadm4 and MAG or Cadm4 and Caspr resulted in the formation of multimyelinated axons due to overgrowth of the myelin away from the axon and the forming paranodal junction. Consequently, these mice displayed paranodal loops either above or underneath compact myelin. Our results demonstrate that accurate placement of the myelin sheath by oligodendrocytes requires the coordinated action of internodal and paranodal CAMs.Oligodendrocyte-axon contact is mediated by several cell adhesion molecules (CAMs) that are positioned at distinct sites along the myelin unit, yet their role during myelination remains unclear. Cadm4 and its axonal receptors, Cadm2 and Cadm3, as well as myelin-associated glycoprotein (MAG), are enriched at the internodes below the compact myelin, whereas NF155, which binds the axonal Caspr/contactin complex, is located at the paranodal junction that is formed between the axon and the terminal loops of the myelin sheath. Here we report that Cadm4-, MAG-, and Caspr-mediated adhesion cooperate during myelin membrane ensheathment. Genetic deletion of either Cadm4 and MAG or Cadm4 and Caspr resulted in the formation of multimyelinated axons due to overgrowth of the myelin away from the axon and the forming paranodal junction. Consequently, these mice displayed paranodal loops either above or underneath compact myelin. Our results demonstrate that accurate placement of the myelin sheath by oligodendrocytes requires the coordinated action of internodal and paranodal CAMs.
Oligodendrocyte-axon contact is mediated by several cell adhesion molecules (CAMs) that are positioned at distinct sites along the myelin unit, yet their role during myelination remains unclear. Cadm4 and its axonal receptors, Cadm2 and Cadm3, as well as myelin-associated glycoprotein (MAG), are enriched at the internodes below the compact myelin, whereas NF155, which binds the axonal Caspr/contactin complex, is located at the paranodal junction that is formed between the axon and the terminal loops of the myelin sheath. Here we report that Cadm4-, MAG-, and Caspr-mediated adhesion cooperate during myelin membrane ensheathment. Genetic deletion of either Cadm4 and MAG or Cadm4 and Caspr resulted in the formation of multimyelinated axons due to overgrowth of the myelin away from the axon and the forming paranodal junction. Consequently, these mice displayed paranodal loops either above or underneath compact myelin. Our results demonstrate that accurate placement of the myelin sheath by oligodendrocytes requires the coordinated action of internodal and paranodal CAMs.
Author Vainshtein, Anya
Peles, Elior
Elazar, Nimrod
Tsoory, Michael
Eshed-Eisenbach, Yael
Rechav, Katya
Author_xml – sequence: 1
  givenname: Nimrod
  surname: Elazar
  fullname: Elazar, Nimrod
  organization: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
– sequence: 2
  givenname: Anya
  surname: Vainshtein
  fullname: Vainshtein, Anya
  organization: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
– sequence: 3
  givenname: Katya
  orcidid: 0000-0003-4664-5704
  surname: Rechav
  fullname: Rechav, Katya
  organization: Electron Microscopy Unit, Weizmann Institute of Science, Rehovot, Israel
– sequence: 4
  givenname: Michael
  surname: Tsoory
  fullname: Tsoory, Michael
  organization: Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel
– sequence: 5
  givenname: Yael
  surname: Eshed-Eisenbach
  fullname: Eshed-Eisenbach, Yael
  organization: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
– sequence: 6
  givenname: Elior
  orcidid: 0000-0002-3325-0597
  surname: Peles
  fullname: Peles, Elior
  email: peles@weizmann.ac.il
  organization: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel peles@weizmann.ac.il
BackLink https://www.ncbi.nlm.nih.gov/pubmed/31451613$$D View this record in MEDLINE/PubMed
BookMark eNpNkDlPAzEQRi0EIgeUtMglzYbxtbFLFHFJkWigXvmEjXbtYO8W--9JRJCo5ht9700xC3QeU_QI3RBYEZDsfmfNigJRUINSZ2hOBIdKEg7n__IMLUrZAQBfc3aJZoxwQWrC5qjZpJRdG_XgHW7j4HNMTndYR4f3OuvT5r58aVPENsUhp65gbe2YDxLuJ98d9WNrJpy69jM5H11Odhp8uUIXQXfFX5_mEn08Pb5vXqrt2_Pr5mFbWS7JUAUQXgRrqXA8SEVVHcAoAoYwAcyB1j6sZZCCmwOoQ1CMmqB4rYIEGyhdorvfu_ucvkdfhqZvi_Vdp6NPY2kolYQAE4oc0NsTOpreu2af217nqfl7Cv0BCVpniQ
CitedBy_id crossref_primary_10_1002_glia_24680
crossref_primary_10_1101_cshperspect_a041361
crossref_primary_10_1186_s11556_025_00371_0
crossref_primary_10_3390_ijms24119361
crossref_primary_10_1523_JNEUROSCI_2736_20_2020
crossref_primary_10_3390_life11030231
crossref_primary_10_3390_ph17111417
crossref_primary_10_7554_eLife_82111
crossref_primary_10_1083_jcb_202204098
crossref_primary_10_1083_jcb_201907077
crossref_primary_10_3389_fcell_2020_00483
crossref_primary_10_4103_1673_5374_300459
crossref_primary_10_1016_j_devcel_2019_11_018
crossref_primary_10_1177_17590914221097510
crossref_primary_10_1002_glia_24614
crossref_primary_10_1016_j_gene_2023_147713
crossref_primary_10_1111_jns_12568
crossref_primary_10_3390_life11020136
crossref_primary_10_1038_s41583_020_00406_8
crossref_primary_10_1038_s41598_021_86673_6
crossref_primary_10_1016_j_devcel_2019_10_016
crossref_primary_10_1038_s41467_022_34302_9
crossref_primary_10_1073_pnas_2218823120
crossref_primary_10_3390_brainsci12040476
crossref_primary_10_1002_glia_24290
crossref_primary_10_1186_s12964_023_01142_z
crossref_primary_10_1096_fj_202101468RRRR
crossref_primary_10_3389_fcell_2022_951809
crossref_primary_10_1038_s41392_024_01971_5
ContentType Journal Article
Copyright 2019 Elazar et al.
Copyright_xml – notice: 2019 Elazar et al.
DBID CGR
CUY
CVF
ECM
EIF
NPM
7X8
DOI 10.1083/jcb.201906099
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
MEDLINE - Academic
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
MEDLINE - Academic
DatabaseTitleList MEDLINE - Academic
MEDLINE
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: 7X8
  name: MEDLINE - Academic
  url: https://search.proquest.com/medline
  sourceTypes: Aggregation Database
DeliveryMethod no_fulltext_linktorsrc
Discipline Biology
EISSN 1540-8140
ExternalDocumentID 31451613
Genre Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural
GrantInformation_xml – fundername: NINDS NIH HHS
  grantid: R01 NS097428
GroupedDBID ---
-DZ
-~X
.55
123
18M
29K
2WC
34G
36B
39C
4.4
53G
85S
ABDNZ
ABOCM
ABPPZ
ABRJW
ABZEH
ACGFO
ACGOD
ACIWK
ACKOT
ACNCT
ACPRK
ADBBV
AEILP
AENEX
AFOSN
AFRAH
ALMA_UNASSIGNED_HOLDINGS
AOIJS
BAWUL
BKOMP
BTFSW
C45
CGR
CS3
CUY
CVF
D-I
D0L
DIK
DU5
E3Z
EBS
ECM
EIF
EJD
EMB
F5P
F9R
FRP
GX1
H13
HF~
HYE
IH2
JZ9
KQ8
N9A
NHB
NPM
O5R
O5S
OK1
P2P
PQQKQ
R.V
RHF
RHI
RNS
RPM
RXW
SJN
TAE
TN5
TR2
TRP
TWZ
UBX
UHB
UKR
UPT
VQA
W8F
WH7
WOQ
X7M
YIN
YKV
YNH
YOC
YQT
YSK
YWH
YZZ
ZCA
~KM
7X8
ID FETCH-LOGICAL-c481t-f05e5fcc25d4f89296f0b910b13503d0aaef78f854b5e5aff932bf9469f80cf22
IEDL.DBID 7X8
ISICitedReferencesCount 39
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000484039900012&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN 1540-8140
IngestDate Thu Sep 04 15:58:30 EDT 2025
Wed Feb 19 02:30:50 EST 2025
IsDoiOpenAccess false
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 9
Language English
License 2019 Elazar et al.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c481t-f05e5fcc25d4f89296f0b910b13503d0aaef78f854b5e5aff932bf9469f80cf22
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ORCID 0000-0003-4664-5704
0000-0002-3325-0597
OpenAccessLink https://rupress.org/jcb/article-pdf/218/9/2887/1264979/jcb_201906099.pdf
PMID 31451613
PQID 2281103591
PQPubID 23479
ParticipantIDs proquest_miscellaneous_2281103591
pubmed_primary_31451613
PublicationCentury 2000
PublicationDate 2019-09-02
PublicationDateYYYYMMDD 2019-09-02
PublicationDate_xml – month: 09
  year: 2019
  text: 2019-09-02
  day: 02
PublicationDecade 2010
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle The Journal of cell biology
PublicationTitleAlternate J Cell Biol
PublicationYear 2019
References 31451614 - J Cell Biol. 2019 Sep 2;218(9):2824-2825
References_xml – reference: 31451614 - J Cell Biol. 2019 Sep 2;218(9):2824-2825
SSID ssj0004743
Score 2.478703
Snippet Oligodendrocyte-axon contact is mediated by several cell adhesion molecules (CAMs) that are positioned at distinct sites along the myelin unit, yet their role...
SourceID proquest
pubmed
SourceType Aggregation Database
Index Database
StartPage 2887
SubjectTerms Animals
Axons - metabolism
Cell Adhesion - genetics
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Cell Adhesion Molecules, Neuronal - genetics
Cell Adhesion Molecules, Neuronal - metabolism
Intercellular Junctions - genetics
Intercellular Junctions - metabolism
Mice
Mice, Knockout
Myelin Sheath - genetics
Myelin Sheath - metabolism
Myelin-Associated Glycoprotein - genetics
Myelin-Associated Glycoprotein - metabolism
Oligodendroglia - cytology
Oligodendroglia - metabolism
Title Coordinated internodal and paranodal adhesion controls accurate myelination by oligodendrocytes
URI https://www.ncbi.nlm.nih.gov/pubmed/31451613
https://www.proquest.com/docview/2281103591
Volume 218
WOSCitedRecordID wos000484039900012&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText
inHoldings 1
isFullTextHit
isPrint
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8QwEA7qKnjx_VhfRPBatk2abnoSWVw86LIHhb2VPLGi7Wp3hf33TtIsehLBS6CQQpmZTr555BuErpTIeGIpjWSe2yiVnIEfNLAoZbLYZJoYT5l_3x-N-GSSj0PCrQltlUuf6B21rpXLkfcI4XBSUZYn19P3yE2NctXVMEJjFXUoQBln1f3JD7bw0GDviv-O2SlwbALq6L0o6fq68jiL81_QpT9lhtv__b4dtBXwJb5pDWIXrZhqD220EycX-6gY1BBtlhUgTI1Lnw2sNewXlcaOBTw86Wfjsmg4NLI3WCg1d6QS-G3hLrB7dWK5wPVrCYGtcawHagGo9QA9DW8fB3dRmLEQqZQns8jGzDCrFGE6tRywUmZjCRBCJpTFVMdCGNvnlrNUwkZhLeA9aXMIqi2PlSXkEK1VdWWOEebaKtC4oFqpVDORCwAvOuUypTIj2nbR5VJyBdiwK0yIytTzpviWXRcdteIvpi3ZRkH9KOGEnvzh7VO06XTqW8DIGepY-IPNOVpXn7Oy-bjwxgHraPzwBZK-x1M
linkProvider ProQuest
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Coordinated+internodal+and+paranodal+adhesion+controls+accurate+myelination+by+oligodendrocytes&rft.jtitle=The+Journal+of+cell+biology&rft.au=Elazar%2C+Nimrod&rft.au=Vainshtein%2C+Anya&rft.au=Rechav%2C+Katya&rft.au=Tsoory%2C+Michael&rft.date=2019-09-02&rft.eissn=1540-8140&rft.volume=218&rft.issue=9&rft.spage=2887&rft_id=info:doi/10.1083%2Fjcb.201906099&rft_id=info%3Apmid%2F31451613&rft_id=info%3Apmid%2F31451613&rft.externalDocID=31451613
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1540-8140&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1540-8140&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1540-8140&client=summon