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Alternative splicing of clathrin heavy chain contributes to the switch from coated pits to plaques
- Source :
- Journal of Cell Biology, Journal of Cell Biology, 2020, 219 (9), ⟨10.1083/jcb.201912061⟩, Journal of Cell Biology, Rockefeller University Press, 2020, 219 (9), ⟨10.1083/jcb.201912061⟩, The Journal of Cell Biology
- Publication Year :
- 2020
- Publisher :
- HAL CCSD, 2020.
-
Abstract
- A single alternatively spliced exon in the CLTC gene contributes to clathrin coat organization. This event participates in the plasticity from clathrin-coated pits to plaques, structures that are essential for muscle fiber function and maintenance.<br />Clathrin function directly derives from its coat structure, and while endocytosis is mediated by clathrin-coated pits, large plaques contribute to cell adhesion. Here, we show that the alternative splicing of a single exon of the clathrin heavy chain gene (CLTC exon 31) helps determine the clathrin coat organization. Direct genetic control was demonstrated by forced CLTC exon 31 skipping in muscle cells that reverses the plasma membrane content from clathrin plaques to pits and by promoting exon inclusion that stimulated flat plaque assembly. Interestingly, mis-splicing of CLTC exon 31 found in the severe congenital form of myotonic dystrophy was associated with reduced plaques in patient myotubes. Moreover, forced exclusion of this exon in WT mice muscle induced structural disorganization and reduced force, highlighting the contribution of this splicing event for the maintenance of tissue homeostasis. This genetic control on clathrin assembly should influence the way we consider how plasticity in clathrin-coated structures is involved in muscle development and maintenance.<br />Graphical Abstract
- Subjects :
- Adult
Male
Physiology
[SDV]Life Sciences [q-bio]
Muscle Fibers, Skeletal
Development
Endocytosis
Clathrin
Clathrin coat
Article
Mice
Young Adult
03 medical and health sciences
Exon
0302 clinical medicine
Animals
Humans
Child
Tissue homeostasis
030304 developmental biology
0303 health sciences
Trafficking
biology
Cell Membrane
Alternative splicing
Coated Pits, Cell-Membrane
Exons
Cell Biology
Cell biology
Mice, Inbred C57BL
[SDV] Life Sciences [q-bio]
Alternative Splicing
Clathrin Heavy Chains
RNA splicing
biology.protein
Female
CLTC
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 00219525 and 15408140
- Database :
- OpenAIRE
- Journal :
- Journal of Cell Biology, Journal of Cell Biology, 2020, 219 (9), ⟨10.1083/jcb.201912061⟩, Journal of Cell Biology, Rockefeller University Press, 2020, 219 (9), ⟨10.1083/jcb.201912061⟩, The Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....86cd348107004a017c7a447877e768f7