ArticleMolecular biology of the cell2012
Connecdenn 3/DENND1C binds actin linking Rab35 activation to the actin cytoskeleton.
Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 56 citations in OpenAlex.
- Evolutionarily conserved short linear motifs drive actin filament binding.Nature cell biology · 2026Article
- Construction of a Prognostic Model for Lung Adenocarcinoma Based on Necrosis by Sodium Overload-Related Genes and Identification of DENND1C as a New Prognostic Marker.Current issues in molecular biology · 2026Article
- Exploring the role of alternative splicing in the pathogenesis of Sjögren's syndrome: identification of novel isoforms associated with salivary gland immune infiltration.Genes & genomics · 2025Article
- Identification of Progression-Associated Biomarkers in Lung Cancer Based on the Integrated Analysis of RNA Sequencing Data From Platelets and Tumor Tissues.International journal of genomics · 2025Article
- Rab35 Is Required for Embryonic Development and Kidney and Ureter Homeostasis through Regulation of Epithelial Cell Junctions.Journal of the American Society of Nephrology : JASN · 2024Article
- Review
- PCSK9 facilitates melanoma pathogenesis via a network regulating tumor immunity.Journal of experimental & clinical cancer research : CR · 2023Article
- Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer.Molecular cancer · 2022Review
- Rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis.Nature communications · 2022Article
- A cell-based GEF assay reveals new substrates for DENN domains and a role for DENND2B in primary ciliogenesis.Science advances · 2022Article
- Rab GTPases: The principal players in crafting the regulatory landscape of endosomal trafficking.Computational and structural biotechnology journal · 2022Review
- Roles for 3' Phosphoinositides in Macropinocytosis.Sub-cellular biochemistry · 2022Article
- Anisotropic expansion of hepatocyte lumina enforced by apical bulkheads.The Journal of cell biology · 2021Article
- Rab35 regulates skeletogenesis and gastrulation by facilitating actin remodeling and vesicular trafficking.Cells & development · 2021Article
- A novel DENND1B-localized structure found at the basal side of adherent cells.Histochemistry and cell biology · 2021Article
- The role of the oncogenic Rab35 in cancer invasion, metastasis, and immune evasion, especially in leukemia.Small GTPases · 2020Review
- Rab35-regulated lipid turnover by myotubularins represses mTORC1 activity and controls myelin growth.Nature communications · 2020Article
- Rab35-GEFs, DENND1A and folliculin differentially regulate podocalyxin trafficking in two- and three-dimensional epithelial cell cultures.The Journal of biological chemistry · 2020Article
- IL-17A Recruits Rab35 to IL-17R to Mediate PKCα-Dependent Stress Fiber Formation and Airway Smooth Muscle Contractility.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- SCD1 and SCD2 Form a Complex That Functions with the Exocyst and RabE1 in Exocytosis and Cytokinesis.The Plant cell · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The small GTPase Rab35 regulates endosomal membrane trafficking but also recruits effectors that modulate actin assembly and organization. Differentially expressed in normal and neoplastic cells (DENN)-domain proteins are a newly identified class of Rab guanine-nucleotide exchange factors (GEFs) that are grouped into eight families, each activating a common Rab. The members of one family, connecdenn 1-3/DENND1A-C, are all GEFs for Rab35. Why Rab35 requires multiple GEFs is unknown. We demonstrate that connecdenn 3 uses a unique C-terminal motif, a feature not found in connecdenn 1 or 2, to directly bind actin. This interaction couples Rab35 activation to the actin cytoskeleton, resulting in dramatic changes in cell shape, notably the formation of protrusive membrane extensions. These alterations are specific to Rab35 activated by connecdenn 3 and require both the actin-binding motif and N-terminal DENN domain, which harbors the GEF activity. It was previously demonstrated that activated Rab35 recruits the actin-bundling protein fascin to actin, but the relevant GEF for this activity was unknown. We demonstrate that connecdenn 3 and Rab35 colocalize with fascin and actin filaments, suggesting that connecdenn 3 is the relevant GEF. Thus, whereas connecdenn 1 and 2 activate Rab35 for endosomal trafficking, connecdenn 3 uniquely activates Rab35 for its role in actin regulation.
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