Dataset Information

Caspr2 interacts with type 1 inositol 1,4,5-trisphosphate receptor in the developing cerebellum and regulates Purkinje cell morphology

ABSTRACT: Contactin-associated protein-like 2 (Caspr2) is a neurexin-like protein that has been associated with numerous neurological conditions. However, the mechanisms underlying Caspr2 function in the central nervous system remain incompletely understood. Here, we report on a functional role for Caspr2 in the developing cerebellum. Loss of Caspr2 impairs Purkinje cell dendritic development, alters cell signaling and results in motor coordination deficits. Caspr2 is highly enriched at synaptic specializations in the cerebellum. Using a proteomic approach, we identify type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) as a specific synaptic interaction partner of the Caspr2 extracellular domain (ECD) in the molecular layer (ML) of the developing cerebellum. The interaction of Caspr2 ECD with IP3R1 inhibits IP3R1-mediated changes in cellular morphology. Together, our work defines a mechanism by which Caspr2 controls the development and function of the cerebellum, and advances our understanding of how Caspr2 dysfunction might lead to specific brain disorders.

INSTRUMENT(S): amaZon ETD

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cerebellum, Brain

SUBMITTER: Holger Kramer

LAB HEAD: Esther B. E. Becker

PROVIDER: PXD018972 | Pride | 2020-07-13

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	LA_CS-F_24May16_BE4_01_30183.d.zip	Other
	LA_CS1-CS5CS-F_24May16_merged.mgf	Mgf
	LA_CS1-CS5CS-F_24May16_merged.mgf_UPR_mus_musculus.dat	Mgf
	LA_CS1-CS5CS-F_24May16_merged.mgf_UPR_mus_musculus.mzid	Mzid
	LA_CS1_24May16_RA8_01_30163.d.zip	Other

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Caspr2 interacts with type 1 inositol 1,4,5-trisphosphate receptor in the developing cerebellum and regulates Purkinje cell morphology.

Argent Liam L Winter Friederike F Prickett Imogen I Carrasquero-Ordaz Maria M Olsen Abby L AL Kramer Holger H Lancaster Eric E Becker Esther B E EBE

The Journal of biological chemistry 20200716 36

Contactin-associated protein-like 2 (Caspr2) is a neurexin-like protein that has been associated with numerous neurological conditions. However, the specific functional roles that Caspr2 plays in the central nervous system and their underlying mechanisms remain incompletely understood. Here, we report on a functional role for Caspr2 in the developing cerebellum. Using a combination of confocal microscopy, biochemical analyses, and behavioral testing, we show that loss of Caspr2 in the <i>Cntnap2 ...[more]

PMID: 32675284

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