Kinesin-1 promotes post-Golgi trafficking of NCAM140 and NCAM180 to the cell surface

Wobst, Hilke; Schmitz, Brigitte; Schachner, Melitta; Diestel, Simone; Leshchyns’ka, Iryna; Sytnyk, Vladimir

doi:10.1242/jcs.169391

Cited by 15 publications

(15 citation statements)

References 81 publications

(113 reference statements)

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“…Disruption of the interaction between NCAM and KLC1 or KLC1 knockdown using targeted siRNA in CHO cells and mouse cortical neurons results in reduced delivery of NCAM to the cell surface and accumulation of NCAM in the Golgi apparatus. 23 These observations are in agreement with studies in Drosophila showing that the transport and localization of Fasciclin II, an ortholog of NCAM in flies, is affected in kinesin light chain (Klc) mutant larvae, and in larvae with mutated unc-51, a kinase which genetically interacts with Klc in kinesin-mediated axonal transport. 29 The binding site for KLC1 has been mapped to amino acids 748-755 (CGKAGPGA), a region which overlaps with the region previously reported to be important for the sorting of NCAM in MDCK cells.…”

Section: Molecular Mechanisms Of the Intracellular Transport Of Ncam supporting

confidence: 90%

“…21 Experiments with various truncated forms of NCAM indicate that the intracellular domain of NCAM is not required for the delivery of NCAM to the cell surface in various cell types including neurons. 22,23 This observation is probably not surprising since the GPI-anchored NCAM120 is efficiently delivered to the cell surface of neurons. 24 The intracellular domain of NCAM is however exposed for interactions with proteins in the cytosol, suggesting that it may play a regulatory role.…”

Section: Molecular Mechanisms Of the Intracellular Transport Of Ncam mentioning

confidence: 91%

“…29 The binding site for KLC1 has been mapped to amino acids 748-755 (CGKAGPGA), a region which overlaps with the region previously reported to be important for the sorting of NCAM in MDCK cells. 22,23 Interestingly, this region has also been shown to contain the binding site for p21-activated protein kinase (PAK1). 9 PAK1 competes with KLC1 for binding to NCAM, and overexpression of the dominant negative domain of PAK1 inhibits the delivery of NCAM to the cell surface suggesting that it contains the binding site for NCAM.…”

Section: Molecular Mechanisms Of the Intracellular Transport Of Ncam mentioning

confidence: 99%

“…9 PAK1 competes with KLC1 for binding to NCAM, and overexpression of the dominant negative domain of PAK1 inhibits the delivery of NCAM to the cell surface suggesting that it contains the binding site for NCAM. 23 The delivery of NCAM to the cell surface is also reduced when the function of the exocyst complex, a complex involved in the tethering of post-Golgi vesicles to the cell surface plasma membrane, is inhibited. 23 These observations suggest a model, in which kinesin-1 transports NCAM-containing vesicles from the Golgi to the cell surface plasma membrane where the competition between PAK1 and KLC1 promotes the detachment of the vesicles from the motor and their exocyst-dependent fusion with the cell surface membrane (Fig.…”

Section: Molecular Mechanisms Of the Intracellular Transport Of Ncam mentioning

confidence: 99%

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Intracellular transport and cell surface delivery of the neural cell adhesion molecule (NCAM)

Leshchyns’ka¹,

Sytnyk

2015

BioArchitecture

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The neural cell adhesion molecule (NCAM) regulates differentiation and functioning of neurons by accumulating at the cell surface where it mediates the interactions of neurons with the extracellular environment. NCAM also induces a number of intracellular signaling cascades, which coordinate interactions at the cell surface with intracellular processes including changes in gene expression, transport and cytoskeleton remodeling. Since NCAM functions at the cell surface, its transport and delivery to the cell surface play a critical role. Here, we review recent advances in our understanding of the molecular mechanisms of the intracellular transport and cell surface delivery of NCAM. We also discuss the data suggesting a possibility of cross talk between activation of NCAM at the cell surface and the intracellular transport and cell surface delivery of NCAM.

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Section: Molecular Mechanisms Of the Intracellular Transport Of Ncam supporting

confidence: 90%

Section: Molecular Mechanisms Of the Intracellular Transport Of Ncam mentioning

confidence: 91%

Section: Molecular Mechanisms Of the Intracellular Transport Of Ncam mentioning

confidence: 99%

Section: Molecular Mechanisms Of the Intracellular Transport Of Ncam mentioning

confidence: 99%

See 2 more Smart Citations

Intracellular transport and cell surface delivery of the neural cell adhesion molecule (NCAM)

Leshchyns’ka¹,

Sytnyk

2015

BioArchitecture

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“…In this study, we show that KLC1 interacts with WAVE1, (BNIP-2), and protein interacting with APP tail 1 (PAT1) [1,8,10,14,21,22]. In this study, we have identified that WAVE1 interacted with the TPR domain of KLC1.…”

Section: Discussionmentioning

confidence: 71%

The Scaffolding Protein WAVE1 Associates with Kinesin 1 through the Tetratricopeptide Repeat (TPR) Domain of the Kinesin Light Chain (KLC)

Jang¹,

Jeong²,

Urm³

et al. 2016

Journal of Life Science

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Kinesin superfamily proteins (KIFs) are microtubule-dependent molecular motor proteins essential for the intracellular transport of organelles and protein complexes in cells. Kinesin 1 is a member of those KIFs that transport various cargoes, including organelles, synaptic vesicles, neurotransmitter receptors, cell signaling molecules, and mRNAs through interaction between its light chain subunit and the cargoes. Kinesin light chains (KLCs) are non-motor subunits that associate with the kinesin heavy chain (KHC) dimer. KLCs interact with many different binding proteins, but their particular binding proteins have not yet been fully identified. We used the yeast two-hybrid assay to identify proteins that interact with the tetratricopeptide repeat (TPR) domain of KLC1. We found an interaction between the TPR domain of KLC1 and Wiskott-Aldrich syndrome protein family member 1 (WAVE1), a member of the WASP/WAVE family involved in regulation of actin cytoskeleton. WAVE1 bound to the six TPR domain-containing regions of KLC1 and did not interact with KHCs (KIF5A, KIF5B, and KIF5C) in the yeast two-hybrid assay. The carboxyl (C)-terminal verprolin-cofilin-acidic (VCA) domain of WAVE1 is essential for interaction with KLC1. Also, other WAVE isoforms (WAVE2 and WAVE3) interacted with KLC1 in the yeast two-hybrid assay. When co-expressed in HEK-293T cells, WAVE1 co-localized with KLC1 and co-immunoprecipitated with KLC1 and KIF5B. These results suggest that kinesin 1 motor protein may transport WAVE complexes or WAVE-coated cargoes in cells.

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The BACE1-generated C-terminal fragment of the neural cell adhesion molecule 2 (NCAM2) promotes BACE1 targeting to Rab11-positive endosomes

Keable

Pfundstein

et al. 2022

Cell. Mol. Life Sci.

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Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), also known as β-secretase, is an aspartic protease. The sorting of this enzyme into Rab11-positive recycling endosomes regulates the BACE1-mediated cleavage of its substrates, however, the mechanisms underlying this targeting remain poorly understood. The neural cell adhesion molecule 2 (NCAM2) is a substrate of BACE1. We show that BACE1 cleaves NCAM2 in cultured hippocampal neurons and NCAM2-transfected CHO cells. The C-terminal fragment of NCAM2 that comprises the intracellular domain and a small portion of NCAM2’s extracellular domain, associates with BACE1. This association is not affected in cells with inhibited endocytosis, indicating that the interaction of NCAM2 and BACE1 precedes the targeting of BACE1 from the cell surface to endosomes. In neurons and CHO cells, this fragment and BACE1 co-localize in Rab11-positive endosomes. Overexpression of full-length NCAM2 or a recombinant NCAM2 fragment containing the transmembrane and intracellular domains but lacking the extracellular domain leads to an increase in BACE1 levels in these organelles. In NCAM2-deficient neurons, the levels of BACE1 are increased at the cell surface and reduced in intracellular organelles. These effects are correlated with increased levels of the soluble extracellular domain of BACE1 in the brains of NCAM2-deficient mice, suggesting increased shedding of BACE1 from the cell surface. Of note, shedding of the extracellular domain of Sez6, a protein cleaved exclusively by BACE1, is reduced in NCAM2-deficient animals. These results indicate that the BACE1-generated fragment of NCAM2 regulates BACE1 activity by promoting the targeting of BACE1 to Rab11-positive endosomes.

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Kinesin-1 promotes post-Golgi trafficking of NCAM140 and NCAM180 to the cell surface

Cited by 15 publications

References 81 publications

Intracellular transport and cell surface delivery of the neural cell adhesion molecule (NCAM)

Intracellular transport and cell surface delivery of the neural cell adhesion molecule (NCAM)

The Scaffolding Protein WAVE1 Associates with Kinesin 1 through the Tetratricopeptide Repeat (TPR) Domain of the Kinesin Light Chain (KLC)

The BACE1-generated C-terminal fragment of the neural cell adhesion molecule 2 (NCAM2) promotes BACE1 targeting to Rab11-positive endosomes

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