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Dynamin Inhibitors Impair Endocytosis and Mitogenic Signaling of PDGF
Laboratory of Cell Biology, International Institute of Molecular and Cell Biology, Warsaw, Poland.
Laboratory of Cell Biology, International Institute of Molecular and Cell Biology, Warsaw, Poland.
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2013 (English)In: Traffic: the International Journal of Intracellular Transport, ISSN 1398-9219, E-ISSN 1600-0854, Vol. 14, no 6, 725-736 p.Article in journal (Refereed) Published
Abstract [en]

Platelet-derived growth factor (PDGF) isoforms regulate cell proliferation, migration and differentiation both in embryonic development and adult tissue remodeling. At the cellular level, growth-factor signaling is often modulated by endocytosis. Despite important functions of PDGF, its endocytosis remains poorly studied, mainly for lack of tools to track internalized ligand by microscopy. Here, we developed such a tool and quantitatively analyzed internalization and endosomal trafficking of PDGF-BB in human fibroblasts. We further show that PDGF can be internalized in the presence of dynamin inhibitors, arguing that both dynamin-dependent and dynamin-independent pathways can mediate PDGF uptake. Although these routes operate with somewhat different kinetics, they both ultimately lead to lysosomal degradation of PDGF. Although acute inhibition of dynamin activity only moderately affects PDGF endocytosis, it specifically decreases downstream signaling of PDGF via signal transducer and activator of transcription 3 (STAT3). This correlates with reduced expression of MYC and impaired cell entry into S-phase, indicating that dynamin activity is required for PDGF-induced mitogenesis. Our data support a general view that the components governing endocytic trafficking may selectively regulate certain signaling effectors activated by a growth factor.

Place, publisher, year, edition, pages
John Wiley & Sons, 2013. Vol. 14, no 6, 725-736 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-201953DOI: 10.1111/tra.12061ISI: 000319230000011PubMedID: 23425318OAI: oai:DiVA.org:uu-201953DiVA: diva2:630170
Available from: 2013-06-18 Created: 2013-06-18 Last updated: 2013-07-25Bibliographically approved

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Publisher's full textPubMedhttp://onlinelibrary.wiley.com/doi/10.1111/tra.12061/pdf

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Heldin, Carl-Henrik
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Ludwig Institute for Cancer ResearchScience for Life Laboratory, SciLifeLab
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