Abstract
The mechanisms coordinating adhesion, actin organization, and membrane traffic during growth cone migration are poorly understood. Neuritogenesis and branching from retinal neurons are regulated by the Rac1B/Rac3 GTPase. We have identified a functional connection between ADP-ribosylation factor (Arf) 6 and p95-APP1 during the regulation of Rac1B-mediated neuritogenesis. P95-APP1 is an ADP-ribosylation factor GTPase-activating protein (ArfGAP) of the GIT family expressed in the developing nervous system. We show that Arf6 has a predominant role in neurite extension compared with Arf1 and Arf5. Cotransfection experiments indicate a specific and cooperative potentiation of neurite extension by Arf6 and the carboxy-terminal portion of p95-APP1. Localization studies in neurons expressing different p95-derived constructs show a codistribution of p95-APP1 with Arf6, but not Arf1. Moreover, p95-APP1-derived proteins with a mutated or deleted ArfGAP domain prevent Rac1B-induced neuritogenesis, leading to PIX-mediated accumulation at large Rab11-positive endocytic vesicles. Our data support a role of p95-APP1 as a specific regulator of Arf6 in the control of membrane trafficking during neuritogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP-Ribosylation Factor 6
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ADP-Ribosylation Factors / metabolism*
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Adaptor Proteins, Signal Transducing
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Animals
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Cycle Proteins / metabolism*
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Chick Embryo
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Endosomes / metabolism
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GTPase-Activating Proteins / chemistry
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GTPase-Activating Proteins / genetics
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GTPase-Activating Proteins / metabolism*
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Guanine Nucleotide Exchange Factors / metabolism*
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Macromolecular Substances
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Mutation
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Nervous System / embryology
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Nervous System / metabolism
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Neurites / metabolism*
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Neurites / ultrastructure*
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Neuropeptides / metabolism*
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Phosphoproteins*
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Protein Structure, Tertiary
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Retina / cytology
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Retina / metabolism
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Rho Guanine Nucleotide Exchange Factors
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Transfection
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rac GTP-Binding Proteins / metabolism*
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rac1 GTP-Binding Protein
Substances
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ADP-Ribosylation Factor 6
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Cell Cycle Proteins
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GIT1 protein, human
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GTPase-Activating Proteins
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Guanine Nucleotide Exchange Factors
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Macromolecular Substances
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Neuropeptides
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Phosphoproteins
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RAC1 protein, human
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Recombinant Proteins
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Rho Guanine Nucleotide Exchange Factors
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ADP-Ribosylation Factors
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ARF6 protein, human
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rac GTP-Binding Proteins
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rac1 GTP-Binding Protein