ArticleMolecular biology of the cell2003
Intersectin 1L guanine nucleotide exchange activity is regulated by adjacent src homology 3 domains that are also involved in endocytosis.
Article in Molecular biology of the cell, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 59 citations in OpenAlex.
- A Systematic Compilation of Human SH3 Domains: A Versatile Superfamily in Cellular Signaling.Cells · 2023Review
- Golgi Apparatus: A Potential Therapeutic Target for Autophagy-Associated Neurological Diseases.Frontiers in cell and developmental biology · 2020Review
- Functional recruitment of dynamin requires multimeric interactions for efficient endocytosis.Nature communications · 2019Article
- Inhibition of Cdc42-intersectin interaction by small molecule ZCL367 impedes cancer cell cycle progression, proliferation, migration, and tumor growth.Cancer biology & therapy · 2019Article
- Intersectin-1s deficiency in pulmonary pathogenesis.Respiratory research · 2017Review
- CDC-42 Orients Cell Migration during Epithelial Intercalation in the Caenorhabditis elegans Epidermis.PLoS genetics · 2016Article
- Host endoplasmic reticulum COPII proteins control cell-to-cell spread of the bacterial pathogen Listeria monocytogenes.Cellular microbiology · 2015Article
- Emerging roles for intersectin (ITSN) in regulating signaling and disease pathways.International journal of molecular sciences · 2013Review
- Intersectin 1 enhances Cbl ubiquitylation of epidermal growth factor receptor through regulation of Sprouty2-Cbl interaction.Molecular and cellular biology · 2012Article
- The endocytic adaptor proteins of pathogenic fungi: charting new and familiar pathways.Medical mycology · 2011Review
- Control of synapse development and plasticity by Rho GTPase regulatory proteins.Progress in neurobiology · 2011Review
- Compartmentalized Ras proteins transform NIH 3T3 cells with different efficiencies.Molecular and cellular biology · 2011Article
- Intersecting pathways in cell biology.Science signaling · 2010Review
- Autoinhibition of GEF activity in Intersectin 1 is mediated by the short SH3-DH domain linker.Protein science : a publication of the Protein Society · 2010Article
- The minimal autoinhibited unit of the guanine nucleotide exchange factor intersectin.PloS one · 2010Article
- Pleiotropic function of intersectin homologue Cin1 in Cryptococcus neoformans.Molecular microbiology · 2010Article
- Intersectin regulates dendritic spine development and somatodendritic endocytosis but not synaptic vesicle recycling in hippocampal neurons.The Journal of biological chemistry · 2009Article
- Role of the C-terminal SH3 domain and N-terminal tyrosine phosphorylation in regulation of Tim and related Dbl-family proteins.Biochemistry · 2008Article
- Article
- Caenorhabditis elegans intersectin: a synaptic protein regulating neurotransmission.Molecular biology of the cell · 2007Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Intersectin 1L is a scaffolding protein involved in endocytosis that also has guanine nucleotide exchange activity for Cdc42. In the context of the full-length protein, the catalytic exchange activity of the DH domain is repressed. Here we use biochemical methods to dissect the mechanism for this inhibition. We demonstrate that the intersectin 1L SH3 domains, which bind endocytic proteins, directly inhibit the activity of the DH domain in assays for both binding and exchange of Cdc42. This inhibitory mechanism seems to act through steric hindrance of Cdc42 binding by an intramolecular interaction between the intersectin 1L SH3 domain region and the adjacent DH domain. Surprisingly, the mode of SH3 domain binding is other than through the proline peptide binding pocket. The dual role of the SH3 domains in endocytosis and repression of exchange activity suggests that the intersectin 1L exchange activity is regulated by endocytosis. We show that the endocytic protein, dynamin, competes for binding to the SH3 domains with the neural Wiskott-Aldrich Syndrome protein, an actin filament nucleation protein that is a substrate for activated Cdc42. Swapping of SH3 domain binding partners might act as a switch controlling the actin nucleation activity of intersectin 1L.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.