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Endoglycan (PODXL2) is proteolytically processed by ADAM10 (a disintegrin and metalloprotease 10) and controls neurite branching in primary neurons
- Source :
- The FASEB journal 35(9), e21813 (2021). doi:10.1096/fj.202100475R, FASEB J. 35:e21813 (2021)
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- Cell adhesion is tightly controlled in multicellular organisms, for example, through proteolytic ectodomain shedding of the adhesion-mediating cell surface transmembrane proteins. In the brain, shedding of cell adhesion proteins is required for nervous system development and function, but the shedding of only a few adhesion proteins has been studied in detail in the mammalian brain. One such adhesion protein is the transmembrane protein endoglycan (PODXL2), which belongs to the CD34-family of highly glycosylated sialomucins. Here, we demonstrate that endoglycan is broadly expressed in the developing mouse brains and is proteolytically shed in vitro in mouse neurons and in vivo in mouse brains. Endoglycan shedding in primary neurons was mediated by the transmembrane protease a disintegrin and metalloprotease 10 (ADAM10), but not by its homolog ADAM17. Functionally, endoglycan deficiency reduced the branching of neurites extending from primary neurons in vitro, whereas deletion of ADAM10 had the opposite effect and increased neurite branching. Taken together, our study discovers a function for endoglycan in neurite branching, establishes endoglycan as an ADAM10 substrate and suggests that ADAM10 cleavage of endoglycan may contribute to neurite branching.
- Subjects :
- Male
physiology [Cell Adhesion]
ADAM10
Disintegrins
Adam10
Adam17
Podxl2
Neurite Branching
Seizure Protein 6
Cell
seizure protein 6
Biochemistry
Mice
ADAM10 Protein
Neurons
Metalloproteinase
ADAM17
biology
Chemistry
Brain
metabolism [Neurites]
metabolism [Disintegrins]
physiology [Neurogenesis]
Transmembrane protein
ddc
Cell biology
medicine.anatomical_structure
Ectodomain
metabolism [Neurons]
metabolism [ADAM10 Protein]
Female
Biotechnology
Neurite
Neurogenesis
Sialoglycoproteins
ADAM10 protein, human
metabolism [Cell Adhesion Molecules]
neurite branching
ADAM17 Protein
Cell Line
metabolism [ADAM17 Protein]
ddc:570
metabolism [Sialoglycoproteins]
PODXL2
Genetics
medicine
Disintegrin
Cell Adhesion
Neurites
Animals
Humans
Cell adhesion
Molecular Biology
PODXL2 protein, human
Membrane Proteins
metabolism [Amyloid Precursor Protein Secretases]
Mice, Inbred C57BL
HEK293 Cells
metabolism [Brain]
Proteolysis
biology.protein
Amyloid Precursor Protein Secretases
Cell Adhesion Molecules
metabolism [Membrane Proteins]
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- The FASEB journal 35(9), e21813 (2021). doi:10.1096/fj.202100475R, FASEB J. 35:e21813 (2021)
- Accession number :
- edsair.doi.dedup.....0cb52c5f81af11ec46e13c8659da062d
- Full Text :
- https://doi.org/10.1096/fj.202100475R