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The 14-3-3? protein binds to the cell adhesion molecule L1, promotes L1 phosphorylation by CKII and influences L1-dependent neurite outgrowth.

ABSTRACT: BACKGROUND: The cell adhesion molecule L1 is crucial for mammalian nervous system development. L1 acts as a mediator of signaling events through its intracellular domain, which comprises a putative binding site for 14-3-3 proteins. These regulators of diverse cellular processes are abundant in the brain and preferentially expressed by neurons. In this study, we investigated whether L1 interacts with 14-3-3 proteins, how this interaction is mediated, and whether 14-3-3 proteins influence the function of L1. METHODOLOGY/PRINCIPAL FINDINGS: By immunoprecipitation, we demonstrated that 14-3-3 proteins are associated with L1 in mouse brain. The site of 14-3-3 interaction in the L1 intracellular domain (L1ICD), which was identified by site-directed mutagenesis and direct binding assays, is phosphorylated by casein kinase II (CKII), and CKII phosphorylation of the L1ICD enhances binding of the 14-3-3 zeta isoform (14-3-3?). Interestingly, in an in vitro phosphorylation assay, 14-3-3? promoted CKII-dependent phosphorylation of the L1ICD. Given that L1 phosphorylation by CKII has been implicated in L1-triggered axonal elongation, we investigated the influence of 14-3-3? on L1-dependent neurite outgrowth. We found that expression of a mutated form of 14-3-3?, which impairs interactions of 14-3-3? with its binding partners, stimulated neurite elongation from cultured rat hippocampal neurons, supporting a functional connection between L1 and 14-3-3?. CONCLUSIONS/SIGNIFICANCE: Our results suggest that 14-3-3?, a novel direct binding partner of the L1ICD, promotes L1 phosphorylation by CKII in the central nervous system, and regulates neurite outgrowth, an important biological process triggered by L1.

SUBMITTER: Ramser EM

PROVIDER: S-EPMC2956685 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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The 14-3-3ζ protein binds to the cell adhesion molecule L1, promotes L1 phosphorylation by CKII and influences L1-dependent neurite outgrowth.

Ramser Elisa M EM Wolters Gerrit G Dityateva Galina G Dityatev Alexander A Schachner Melitta M Tilling Thomas T

PloS one 20101018 10

<h4>Background</h4>The cell adhesion molecule L1 is crucial for mammalian nervous system development. L1 acts as a mediator of signaling events through its intracellular domain, which comprises a putative binding site for 14-3-3 proteins. These regulators of diverse cellular processes are abundant in the brain and preferentially expressed by neurons. In this study, we investigated whether L1 interacts with 14-3-3 proteins, how this interaction is mediated, and whether 14-3-3 proteins influence t ...[more]

PMID: 20976158

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Project description:Aligned, electrospun fiber scaffolds provide topographical guidance for regenerating neurons and glia after central nervous system injury. To date, no study has explored how fiber surface nanotopography affects astrocyte response to fibrous scaffolds. Astrocytes play important roles in the glial scar, the blood brain barrier, and in maintaining homeostasis in the central nervous system. In this study, electrospun poly L-lactic acid fibers were engineered with smooth, pitted, or divoted surface nanotopography. Cortical or spinal cord primary rat astrocytes were cultured on the surfaces for either 1 or 3 d to examine the astrocyte response over time. The results showed that cortical astrocytes were significantly shorter and broader on the pitted and divoted fibers compared to those on smooth fibers. However, spinal cord astrocyte morphology was not significantly altered by the surface features. These findings indicate that astrocytes from unique anatomical locations respond differently to the presence of nanotopography. Western blot results show that the differences in morphology were not associated with significant changes in glial fibrillary acidicprotein (GFAP) or vinculin in either astrocyte population, suggesting that surface pits and divots do not induce a reactive phenotype in either cortical or spinal cord astrocytes. Finally, astrocytes were co-cultured with dorsal root ganglia to determine how the surfaces affected astrocyte-mediated neurite outgrowth. Astrocytes cultured on the fibers for shorter periods of time (1 d) generally supported longer neurite outgrowth. Pitted and divoted fibers restricted spinal cord astrocyte-mediated neurite outgrowth, while smooth fibers increased 3 d spinal cord astrocyte-mediated neurite outgrowth. In total, fiber surface nanotopography can influence astrocyte elongation and influence the capability of astrocytes to direct neurites. Therefore, fiber surface characteristics should be carefully controlled to optimize astrocyte-mediated axonal regeneration.

Dataset Information

The 14-3-3? protein binds to the cell adhesion molecule L1, promotes L1 phosphorylation by CKII and influences L1-dependent neurite outgrowth.

Publications

The 14-3-3ζ protein binds to the cell adhesion molecule L1, promotes L1 phosphorylation by CKII and influences L1-dependent neurite outgrowth.

Similar Datasets

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