The subcellular localization of the PDGF β-receptor was investigated in relation with PDGF-induced actin and membrane dynamics in mouse C3H10T1/2 fibroblasts. Serum-starved cells exhibit a nonhomogenous distribution of PDGF β-receptors. However, the observed pattern does not resemble the localization of PDGF-induced actin structures. Interestingly, the PDGF β-receptor showed a changed subcellular distribution in relation to the formation of PDGF-BB-induced actin structures. Upon PDGF exposure, PDGF β-receptors were found to accumulate in dorsal circular ruffles. The presence of both macropinosomes and clathrin in the induced circular ruffles suggests that the accumulation of PDGF β-receptors in circular ruffles results in the efficient internalization of PDGF β-receptors. 1. Introduction One of the most essential proteins involved in cellular dynamics is represented by actin. Actin plays a dominant role in cell motility, morphogenesis, and cell-cell and cell-matrix interactions [1–3]. In addition actin is involved in many local dynamic processes such as the formation of leading edges and membrane ruffle formation [4, 5]. These local actin-driven processes are intriguing with respect to the fact that they can be induced by extracellular signal molecules like polypeptide growth factors. Thus, for example, epidermal growth factor (EGF) has been demonstrated to induce membrane ruffle formation in A431 epidermoid carcinoma cells within 5 minutes after addition of the growth factor [6, 7]. Similarly, platelet-derived growth factor (PDGF) has been demonstrated to induce very typical circular membrane ruffles in fibroblasts [8–10]. The PDGF β-receptor is a tyrosine kinase receptor of ~180？kDa. Each receptor contains five extracellular immunoglobulin-like domains and an intracellular tyrosine kinase domain. PDGF isoforms are dimeric molecules that bind two receptors simultaneously [11]. The complex of the ligand with its receptors is further stabilized by direct receptor-receptor interactions mediated by its extracellular immunoglobulin-like domains. After binding of PDGF by the receptor, the intracellular kinase domains become activated and subsequently phosphorylated, and this is the starting point for various signal transduction cascades. Eventually, these signal transduction cascades activate actin induced membrane ruffling. Other phenomena that were described to originate from PDGF-induced signal transduction cascades are, for example, the increase of intracellular calcium levels and loss of stress fibers. Ultimately, PDGF β-receptor signaling determines
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