ArticlePloS one2014
CLN3 deficient cells display defects in the ARF1-Cdc42 pathway and actin-dependent events.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Reversible synaptic deficits in early-stage batten disease.Journal of translational medicine · 2026Article
- Toward Early Diagnosis and Therapeutic Discovery in CLN3 Disease: A Computational Biomarker Discovery Framework.medRxiv : the preprint server for health sciences · 2026Article
- Loss of CLN3 in microglia leads to impaired lipid metabolism and myelin turnover.Communications biology · 2024Article
- Lysosomal alterations and decreased electrophysiological activity in CLN3 disease patient-derived cortical neurons.Disease models & mechanisms · 2022Article
- Autophagy in the Neuronal Ceroid Lipofuscinoses (Batten Disease).Frontiers in cell and developmental biology · 2022Review
- CLN3, at the crossroads of endocytic trafficking.Neuroscience letters · 2021Article
- Lysosomal dysfunction impairs mitochondrial quality control and is associated with neurodegeneration inBrain communications · 2021Article
- Cellular models of Batten disease.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- The CLN3 gene and protein: What we know.Molecular genetics & genomic medicine · 2019Review
- Article
- Modulating membrane fluidity corrects Batten disease phenotypes in vitro and in vivo.Neurobiology of disease · 2018Article
- Dysregulation of autophagy as a common mechanism in lysosomal storage diseases.Essays in biochemistry · 2017Review
- Aberrant adhesion impacts early development in a Dictyostelium model for juvenile neuronal ceroid lipofuscinosis.Cell adhesion & migration · 2017Article
- DNA methylation in the pathophysiology of hyperphenylalaninemia in the PAH(enu2) mouse model of phenylketonuria.Molecular genetics and metabolism · 2016Article
- Antigen presenting cell abnormalities in the Cln3(-/-) mouse model of juvenile neuronal ceroid lipofuscinosis.Biochimica et biophysica acta · 2016Article
- Lacritin and other autophagy associated proteins in ocular surface health.Experimental eye research · 2016Review
- Photoreceptor phagosome processing defects and disturbed autophagy in retinal pigment epithelium of Cln3Δex1-6 mice modelling juvenile neuronal ceroid lipofuscinosis (Batten disease).Human molecular genetics · 2015Article
- Unbiased Cell-based Screening in a Neuronal Cell Model of Batten Disease Highlights an Interaction between Ca2+ Homeostasis, Autophagy, and CLN3 Protein Function.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Juvenile Batten disease (juvenile neuronal ceroid lipofuscinosis, JNCL) is a devastating neurodegenerative disease caused by mutations in CLN3, a protein of undefined function. Cell lines derived from patients or mice with CLN3 deficiency have impairments in actin-regulated processes such as endocytosis, autophagy, vesicular trafficking, and cell migration. Here we demonstrate the small GTPase Cdc42 is misregulated in the absence of CLN3, and thus may be a common link to multiple cellular defects. We discover that active Cdc42 (Cdc42-GTP) is elevated in endothelial cells from CLN3 deficient mouse brain, and correlates with enhanced PAK-1 phosphorylation, LIMK membrane recruitment, and altered actin-driven events. We also demonstrate dramatically reduced plasma membrane recruitment of the Cdc42 GTPase activating protein, ARHGAP21. In line with this, GTP-loaded ARF1, an effector of ARHGAP21 recruitment, is depressed. Together these data implicate misregulated ARF1-Cdc42 signaling as a central defect in JNCL cells, which in-turn impairs various cell functions. Furthermore our findings support concerted action of ARF1, ARHGAP21, and Cdc42 to regulate fluid phase endocytosis in mammalian cells. The ARF1-Cdc42 pathway presents a promising new avenue for JNCL therapeutic development.
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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.