Dynamin Inhibitors Impair Endocytosis and Mitogenic Signaling of PDGF

Research output: Contribution to journalArticlepeer-review

Standard

Dynamin Inhibitors Impair Endocytosis and Mitogenic Signaling of PDGF. / Sadowski, Lukasz; Jastrzębski, Kamil; Kalaidzidis, Yannis; Heldin, Carl-Henrik; Hellberg, Carina; Miaczynska, Marta; Hellberg, Karina.

In: Traffic, 21.02.2013.

Research output: Contribution to journalArticlepeer-review

Harvard

Sadowski, L, Jastrzębski, K, Kalaidzidis, Y, Heldin, C-H, Hellberg, C, Miaczynska, M & Hellberg, K 2013, 'Dynamin Inhibitors Impair Endocytosis and Mitogenic Signaling of PDGF', Traffic. https://doi.org/10.1111/tra.12061

APA

Sadowski, L., Jastrzębski, K., Kalaidzidis, Y., Heldin, C-H., Hellberg, C., Miaczynska, M., & Hellberg, K. (2013). Dynamin Inhibitors Impair Endocytosis and Mitogenic Signaling of PDGF. Traffic. https://doi.org/10.1111/tra.12061

Vancouver

Sadowski L, Jastrzębski K, Kalaidzidis Y, Heldin C-H, Hellberg C, Miaczynska M et al. Dynamin Inhibitors Impair Endocytosis and Mitogenic Signaling of PDGF. Traffic. 2013 Feb 21. https://doi.org/10.1111/tra.12061

Author

Sadowski, Lukasz ; Jastrzębski, Kamil ; Kalaidzidis, Yannis ; Heldin, Carl-Henrik ; Hellberg, Carina ; Miaczynska, Marta ; Hellberg, Karina. / Dynamin Inhibitors Impair Endocytosis and Mitogenic Signaling of PDGF. In: Traffic. 2013.

Bibtex

@article{ef83482d84dc4801baad35f9d7c453c0,
title = "Dynamin Inhibitors Impair Endocytosis and Mitogenic Signaling of PDGF",
abstract = "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.",
author = "Lukasz Sadowski and Kamil Jastrz{\c e}bski and Yannis Kalaidzidis and Carl-Henrik Heldin and Carina Hellberg and Marta Miaczynska and Karina Hellberg",
note = "{\textcopyright} 2013 John Wiley & Sons A/S.",
year = "2013",
month = feb,
day = "21",
doi = "10.1111/tra.12061",
language = "English",
journal = "Traffic",
issn = "1398-9219",
publisher = "Wiley",

}

RIS

TY - JOUR

T1 - Dynamin Inhibitors Impair Endocytosis and Mitogenic Signaling of PDGF

AU - Sadowski, Lukasz

AU - Jastrzębski, Kamil

AU - Kalaidzidis, Yannis

AU - Heldin, Carl-Henrik

AU - Hellberg, Carina

AU - Miaczynska, Marta

AU - Hellberg, Karina

N1 - © 2013 John Wiley & Sons A/S.

PY - 2013/2/21

Y1 - 2013/2/21

N2 - 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.

AB - 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.

U2 - 10.1111/tra.12061

DO - 10.1111/tra.12061

M3 - Article

C2 - 23425318

JO - Traffic

JF - Traffic

SN - 1398-9219

ER -