Related Experiment Video
Updated: Jun 22, 2026
Isolation of Type I and Type II Pericytes from Mouse Skeletal Muscles
Published on: May 26, 2017
Two different PDGF beta-receptor cohorts in human pericytes mediate distinct biological endpoints
Christian Sundberg1, Tomas Friman, Leah E Hecht
1Department of Orthopaedic Surgery, Children's' Hospital, Boston, Massachusetts 02115, USA.
Abstract:
How activation of a specific growth factor receptor selectively results in either cell proliferation or cytoskeletal reorganization is of central importance to the field of pathophysiology. In this study, we report on a novel mechanism that explains how this process is accomplished. Our current investigation demonstrates that soluble platelet derived growth factor- (PDGF)-BB activates a cohort of PDGF-beta receptors primarily confined to the lipid raft component of the cell membrane, specifically caveolae. In contrast, cell-bound PDGF-BB delivered via cell-cell contact results in activation and the subsequent up-regulation of a cohort of PDGF beta-receptors primarily confined to the non-lipid raft component of the cell membrane. Individual activation of these two receptor cohorts results in distinct biological endpoints, cytoskeletal reorganization or cell proliferation. Mechanistically, our evidence suggests that PDGF-BB-bearing cells preferentially stimulate the non-lipid raft receptor cohort through interleukin 1beta-mediated inhibition of the lipid raft cohort of receptors, leaving the non-raft receptor cohort operational and preferentially stimulated. In human skin injected with PDGF-BB and in tissue reparative processes PDGF beta-receptors colocalize with the caveolae/lipid raft marker caveolin-1. In contrast, in human skin injected with PDGF-BB-bearing tumor cells and in colorectal adenocarcinoma, activated PDGF beta-receptors do not colocalize with caveolin-1. Thus, growth factor receptors are segregated into specific cell membrane compartments that are preferentially activated through different mechanisms of ligand delivery, resulting in distinct biological endpoints.
Insights
Platelet-derived growth factor (PDGF)-BB triggers distinct cell responses. Soluble PDGF-BB activates raft-localized receptors for cytoskeletal changes, while cell-bound PDGF-BB activates non-raft receptors for proliferation.
Area of Science:
- Cell Biology
- Molecular Biology
- Pathophysiology
Background:
- Growth factor receptor activation dictates cell fate, influencing proliferation or cytoskeletal changes.
- Understanding the mechanisms behind differential receptor signaling is crucial for pathophysiology.
Purpose of the Study:
- To elucidate the novel mechanism by which platelet-derived growth factor (PDGF)-BB selectively induces either cell proliferation or cytoskeletal reorganization.
- To investigate the role of receptor localization within cell membrane compartments in mediating distinct biological outcomes.
Main Methods:
- Differential activation of PDGF beta-receptors located in lipid rafts (caveolae) versus non-lipid rafts.
- Investigating the role of interleukin 1 beta in mediating receptor cohort activation.
- Colocalization studies of PDGF beta-receptors with caveolin-1 in various biological contexts (injected skin, tumor cells, adenocarcinoma).
Main Results:
- Soluble PDGF-BB activates raft-associated PDGF beta-receptors, leading to cytoskeletal reorganization.
- Cell-bound PDGF-BB activates non-raft-associated PDGF beta-receptors, promoting cell proliferation.
- Interleukin 1 beta signaling appears to inhibit raft-associated receptors, favoring non-raft activation by cell-bound PDGF-BB.
- PDGF beta-receptors colocalize with caveolin-1 in normal tissue repair but not in tumor contexts.
Conclusions:
- Growth factor receptors are segregated into distinct membrane compartments (lipid rafts vs. non-lipid rafts).
- Ligand delivery mechanisms (soluble vs. cell-bound) preferentially activate specific receptor cohorts.
- This compartmentalization and differential activation dictate distinct cellular responses, impacting pathophysiology and disease, such as cancer.
