ArticleScience advances2022
A cell-based GEF assay reveals new substrates for DENN domains and a role for DENND2B in primary ciliogenesis.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- The role of accessory proteins and co-factors in regulation of melanocortin-4 receptor signalling: An update.Journal of neuroendocrinology · 2026Review
- Variants in DENND2B are associated with vulnerability for neurodevelopmental impairment, psychosis and catatonia.Brain : a journal of neurology · 2026Article
- A tale of Rabs and the exocyst complex in ciliary trafficking and biogenesis.Frontiers in cell and developmental biology · 2025Review
- Dennd2c Negatively Controls Multinucleation and Differentiation in Osteoclasts by Regulating Actin Polymerization and Protrusion Formation.International journal of molecular sciences · 2024Article
- A neurodevelopmental disorder associated with a loss-of-function missense mutation in RAB35.The Journal of biological chemistry · 2024Article
- Hepatitis B virus evades the immune system by suppressing the NF-κB signaling pathway with DENND2A.Microbiology spectrum · 2024Article
- DENND6A links Arl8b to a Rab34/RILP/dynein complex, regulating lysosomal positioning and autophagy.Nature communications · 2024Article
- The LRRK2 signaling network converges on a centriolar phospho-Rab10/RILPL1 complex to cause deficits in centrosome cohesion and cell polarization.Biology open · 2022Article
- 1-L Transcription in Alzheimer's Disease.Current issues in molecular biology · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary cilia are sensory antennae crucial for cell and organism development, and defects in their biogenesis cause ciliopathies. Ciliogenesis involves membrane trafficking mediated by small guanosine triphosphatases (GTPases) including Rabs, molecular switches activated by guanine nucleotide exchange factors (GEFs). The largest family of Rab GEFs is the DENN domain-bearing proteins. Here, we screen all 60 Rabs against two major DENN domain families using a cellular GEF assay, uncovering 19 novel DENN/Rab pairs. The screen reveals Rab10 as a substrate for DENND2B, a protein previously implicated in cancer and severe mental retardation. Through activation of Rab10, DENND2B represses the formation of primary cilia. Through a second pathway, DENND2B functions as a GEF for RhoA to control the length of primary cilia. This work thus identifies an unexpected diversity in DENN domain-mediated activation of Rabs, a previously unidentified non-Rab substrate for a DENN domain, and a new regulatory protein in primary ciliogenesis.
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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.