ArticleMolecular biology of the cell2007
Naked2 acts as a cargo recognition and targeting protein to ensure proper delivery and fusion of TGF-alpha containing exocytic vesicles at the lower lateral membrane of polarized MDCK cells.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- Recent Advances in the Study of Extracellular Vesicles in Colorectal Cancer.Gastroenterology · 2022Review
- NKD2 mediates stimulation-dependent ORAI1 trafficking to augment CaCell reports · 2021Article
- The protein secretion modulator TMED9 drives CNIH4/TGFα/GLI signaling opposing TMED3-WNT-TCF to promote colon cancer metastases.Oncogene · 2019Article
- Protein kinase A-mediated phosphorylation of naked cuticle homolog 2 stimulates cell-surface delivery of transforming growth factor-α for epidermal growth factor receptor transactivation.Traffic (Copenhagen, Denmark) · 2019Article
- Rab 10-a traffic controller in multiple cellular pathways and locations.Journal of cellular physiology · 2018Review
- The EGFR-ADAM17 Axis in Chronic Obstructive Pulmonary Disease and Cystic Fibrosis Lung Pathology.Mediators of inflammation · 2018Review
- Membrane Transport across Polarized Epithelia.Cold Spring Harbor perspectives in biology · 2017Review
- EGF receptor ligands: recent advances.F1000Research · 2016Review
- Up-Regulation of Corticocerebral NKD2 in Lipopolysaccharide-Induced Neuroinflammation.Cellular and molecular neurobiology · 2016Article
- NKD2, a negative regulator of Wnt signaling, suppresses tumor growth and metastasis in osteosarcoma.Oncogene · 2015Article
- Translational profiles of medullary myofibroblasts during kidney fibrosis.Journal of the American Society of Nephrology : JASN · 2014Article
- From wavy hair to naked proteins: the role of transforming growth factor alpha in health and disease.Seminars in cell & developmental biology · 2014Review
- Organization and execution of the epithelial polarity programme.Nature reviews. Molecular cell biology · 2014Review
- Trafficking of epidermal growth factor receptor ligands in polarized epithelial cells.Annual review of physiology · 2014Review
- A monoclonal antibody produced against Naked2.Monoclonal antibodies in immunodiagnosis and immunotherapy · 2013Article
- Barrier disrupting effects of alternaria alternata extract on bronchial epithelium from asthmatic donors.PloS one · 2013Article
- Role of membrane traffic in the generation of epithelial cell asymmetry.Nature cell biology · 2012Review
- Article
- Identification of a novel mono-leucine basolateral sorting motif within the cytoplasmic domain of amphiregulin.Traffic (Copenhagen, Denmark) · 2011Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Transforming growth factor-alpha (TGF-alpha) is the major autocrine EGF receptor ligand in vivo. In polarized epithelial cells, proTGF-alpha is synthesized and then delivered to the basolateral cell surface. We previously reported that Naked2 interacts with basolateral sorting determinants in the cytoplasmic tail of a Golgi-processed form of TGF-alpha and that TGF-alpha is not detected at the basolateral surface of Madin-Darby canine kidney (MDCK) cells expressing myristoylation-deficient (G2A) Naked2. By high-resolution microscopy, we now show that wild-type, but not G2A, Naked2-associated vesicles fuse at the plasma membrane. We further demonstrate that Naked2-associated vesicles are delivered to the lower lateral membrane of polarized MDCK cells independent of mu1B adaptin. We identify a basolateral targeting segment within Naked2; residues 1-173 redirect NHERF-1 from the apical cytoplasm to the basolateral membrane, and internal deletion of residues 37-104 results in apical mislocalization of Naked2 and TGF-alpha. Short hairpin RNA knockdown of Naked2 leads to a dramatic reduction in the 16-kDa cell surface isoform of TGF-alpha and increased cytosolic TGF-alpha immunoreactivity. We propose that Naked2 acts as a cargo recognition and targeting (CaRT) protein to ensure proper delivery, tethering, and fusion of TGF-alpha-containing vesicles to a distinct region at the basolateral surface of polarized epithelial cells.
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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.