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Biochemical characterization of the cellular biosynthesis and trafficking of Caspr2
Author(s) -
Falivelli Giulia,
Davide Comoletti,
Dubi Noga,
De Jaco Antonella,
Wilson Jennifer,
Taylor Palmer
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.839.1
Subject(s) - endoplasmic reticulum , microbiology and biotechnology , mutant , biology , cell , hek 293 cells , phenotype , neuroscience , gene , genetics
Recent genetic studies have linked mutations of Contactin‐associated Protein‐like 2 (Caspr2), a gene product of CNTNAP2, in neurodevelopmental conditions such as autism and epilepsy. Although little information is currently available for the role of this protein in the human brain, recent lines of evidence suggest that Caspr2 is a key molecule in cell‐cell interactions important for normal neuronal function and cortical development. Here, we investigate the processing and trafficking of Caspr2 wild type and several mutants using biochemical and cell biological approaches. Through analysis of glycosylation processing in HEK293 cells, we show that some of the mutations impair Caspr2’s trafficking to its cellular location. Furthermore, analyses of confocal immunofluorescence co‐localization with chaperons like calreticulin demonstrate that certain mutants have increased retention in the endoplasmic reticulum and retarded transport of newly synthesized proteins to the cell surface. These observations promise to yield critical insights into congenital processes that give rise brain abnormalities in neuronal connectivity. This work was supported by: USPHS Grant R37 GM‐18360 and NIEHS to PT, and Autism Speaks #2617 to DC