SUMMARY:
SEPTIN2 but not SEPTIN9 is required for the formation or stabilization of a septin multimer in PNS myelin in vivo.
TITLE:
Targeted inactivation of the Septin2 and Septin9 genes in myelinating Schwann cells of mice
DESCRIPTION:
The formation of axon-enwrapping myelin sheaths by oligodendrocytes in the central nervous system (CNS) involves the assembly of a scaffolding septin filament comprised of the subunits SEPTIN2, SEPTIN4, SEPTIN7 and SEPTIN8. Conversely, in the peripheral nervous system (PNS) myelin is synthesized by a different cell type termed Schwann cells, and it remained unknown if septins also assemble as a multimer in PNS myelin. According to prior proteome analysis, PNS myelin comprises the subunits…
CONTENT:
Cytoskeleton (Hoboken). 2022 Nov 15. doi: 10.1002/cm.21736. Online ahead of print.
ABSTRACT
The formation of axon-enwrapping myelin sheaths by oligodendrocytes in the central nervous system (CNS) involves the assembly of a scaffolding septin filament comprised of the subunits SEPTIN2, SEPTIN4, SEPTIN7 and SEPTIN8. Conversely, in the peripheral nervous system (PNS) myelin is synthesized by a different cell type termed Schwann cells, and it remained unknown if septins also assemble as a multimer in PNS myelin. According to prior proteome analysis, PNS myelin comprises the subunits SEPTIN2, SEPTIN7, SEPTIN8, SEPTIN9 and SEPTIN11, which localize to the paranodal and abaxonal myelin sub-compartments. Here we use the Cre/loxP-system to delete the Septin9-gene specifically in Schwann cells, causing a markedly reduced abundance of SEPTIN9 in sciatic nerves, implying that Schwann cells are the main cell type expressing SEPTIN9 in the nerve. However, Septin9-deficiency in Schwann cells did not affect the abundance or localization of other septin subunits. In contrast, when deleting the Septin2-gene in Schwann cells the abundance of all relevant septin subunits was markedly reduced, including SEPTIN9. Notably, we did not find evidence that deleting Septin2 or Septin9 in Schwann cells impairs myelin biogenesis, nerve conduction velocity or motor/sensory capabilities, at least at the assessed timepoints. Our data thus show that SEPTIN2 but not SEPTIN9 is required for the formation or stabilization of a septin multimer in PNS myelin in vivo; however, its functional relevance remains to be established. This article is protected by copyright. All rights reserved.
PMID:36378242 | DOI:10.1002/cm.21736
SOURCE:
Cytoskeleton (Hoboken, N.J.)
TAGS:
SEPTIN2 SEPTIN9
CATEGORY:
Research
SUBCATEGORY:
n/a
DATE – PUBLISHED:
2022-11-15T16:33:35Z
DATE – DOI: 2022-11-15T16:33:35Z
DATE – PUBMED: 2022 Nov 15
DATE OUTPUT MATCHED: True
DATE – ADDED:
Tue, 15 Nov 2022 06:00:00 -0500
DATE – RETRIEVED:
11/15/22 01:01PM
2022-11-15T13:01:15-05:00
FEATURED IMAGE:
Media Uploaded (image/png)
IDENTIFIER:
pmid:36378242,doi:10.1002/cm.21736
PUBMED ID:
pubmed:36378242
DOI:
10.1002/cm.21736
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36378242/
LINK – DOI:
https://doi.org/10.1002/cm.21736
LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1002/cm.21736
REFERENCES:
CMT Treatment Report, Urgent Research, 2022-11-15T13:01:15-05:00, https://www.cmttreatmentreport.com.
