Cited by 218Cellular transport and secretionProtein Kinase Regulation and GTPase SignalingNeuroscience and Neuropharmacology Research

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Mammalian Scribble Forms a Tight Complex with the βPIX Exchange Factor

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Audebert, Stéphane, Navarro, Christel, Nourry, Claire, Chasserot-Golaz, Sylvette, Lécine, Patrick, Bellaiche, Yohanns, Dupont, Jean-Luc, Premont, Richard T, Sempéré, Christine, Strub, Jean-Marc, Van Dorsselaer, Alain, Vitale, Nicolas, Borg, Jean-Paul·2004·Current Biology

DOI 10.1016/j.cub.2004.05.051

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Abstract

Drosophila Scribble is implicated in the development of normal synapse structure and epithelial tissues, but it remains unclear how it plays a role and which process it controls. The mammalian homolog of Scribble, hScrib, has a primary structure and subcellular localization similar to that of its fly homolog, but its function remains unknown. Here we have used tandem mass spectrometry to identify major components of the hScrib network. We show that it includes betaPIX (also called Cool-1), a guanine nucleotide exchange factor (GEF), and its partner GIT1 (also called p95-APP1), a GTPase activating protein (GAP). betaPIX directly binds to the hScrib PDZ domains, and the hScrib/betaPIX complex is efficiently recovered in epithelial and neuronal cells and tissues. In cerebellar granule cell cultures, hScrib and betaPIX are both partially localized at neuronal presynaptic compartments. Furthermore, we show that hScrib is required to anchor betaPIX at the cell cortex and that dominant-negative betaPIX or hScrib proteins can each inhibit Ca2+-dependent exocytosis in neuroendocrine PC12 cells, demonstrating a functional relationship between these proteins. These data reveal the existence of a tight hScrib/betaPIX interaction and suggest that this complex potentially plays a role in neuronal transmission.

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Authors: Audebert, S., Navarro, C., Nourry, C., Chasserot-Golaz, S., Lécine, P., Bellaiche, Y., Dupont, J.-L., Premont, R. T., Sempéré, C., Strub, J.-M., Van Dorsselaer, A., Vitale, N., & Borg, J.-P.
Affiliations: Inserm (FR)
Centre National de la Recherche Scientifique (FR)
Duke Medical Center (US)
Corresponding author: Borg, Jean-Paul
ORCID: Audebert, Stéphane
Lécine, Patrick
Premont, Richard T
Strub, Jean-Marc
Vitale, Nicolas
Borg, Jean-Paul
Venue: Current Biology
Publisher: Elsevier BV
Published: 2004-06
Volume: 14
Issue: 11
Pages: 987-995
ISSN: 0960-9822 (ISSN-L)
DOI: 10.1016/j.cub.2004.05.051
OpenAlex: W2007101096
Cited by: 218
References: 30
Citations by year: 2025: 1 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 10 · 2020: 9 · 2019: 10 · 2018: 11 · 2017: 10 · 2016: 12 · 2015: 9 · 2014: 15 · 2013: 11 · 2012: 14
FWCI: 5.22
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 3333 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Current Biology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: Scribble, betaPIX, GIT1, PDZ domain, guanine nucleotide exchange factor, GTPase-activating protein, protein-protein interaction, presynaptic complex, exocytosis, neural transmission, cell cortex, cerebellar granule cells, synaptic structure, epithelium
MeSH terms: Cell Membrane, Cells, Cultured, Chromatography, High Pressure Liquid, Electrophoresis, Polyacrylamide Gel, Enzyme-Linked Immunosorbent Assay, Exocytosis, Humans, Membrane Proteins, Phosphoproteins, Precipitin Tests, Mass Spectrometry, Presynaptic Terminals, DNA, Complementary, Cell Cycle Proteins, Reverse Transcriptase Polymerase Chain Reaction, Guanine Nucleotide Exchange Factors, GTPase-Activating Proteins, Two-Hybrid System Techniques, Tumor Suppressor Proteins, Adaptor Proteins, Signal Transducing, Rho Guanine Nucleotide Exchange Factors

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Mammalian Scribble Forms a Tight Complex with the βPIX Exchange Factor

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