Journal
MOLECULAR NEUROBIOLOGY
Volume 57, Issue 5, Pages 2479-2493Publisher
SPRINGER
DOI: 10.1007/s12035-020-01895-5
Keywords
CRIPT; Neuron; Dendrite; Dendritic spine; Morphology; Arborization
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Funding
- National Science Foundation [IOS-1353724] Funding Source: Medline
- NIGMS NIH HHS [K12 GM093854, T32 GM008339] Funding Source: Medline
- NIH HHS [IRACDA (Institutional Research and Career Development Award) INSPIRE - IRACDA2K12GM093854-07A1, Biotechnology Training Grant T32 GM008339-20] Funding Source: Medline
- New Jersey Commission on Brain Injury Research [CBIR19FEL018, CBIR14IRG019] Funding Source: Medline
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CRIPT, the cysteine-rich PDZ-binding protein, binds to the third PDZ domain of PSD-95 (postsynaptic density protein 95) family proteins and directly binds microtubules, linking PSD-95 family proteins to the neuronal cytoskeleton. Here, we show that overexpression of a full-length CRIPT leads to a modest decrease, and knockdown of CRIPT leads to an increase in dendritic branching in cultured rat hippocampal neurons. Overexpression of truncated CRIPT lacking the PDZ domain-binding motif, which does not bind to PSD-95, significantly decreases dendritic arborization. Conversely, overexpression of a full-length CRIPT significantly increases the number of immature and mature dendritic spines, and this effect is not observed when CRIPT increment PDZ is overexpressed. Competitive inhibition of CRIPT binding to the third PDZ domain of PSD-95 with PDZ3-binding peptides resulted in differential effects on dendritic arborization based on the origin of respective peptide sequence. These results highlight multifunctional roles of CRIPT during development and underscore the significance of the interaction between CRIPT and the third PDZ domain of PSD-95.
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