The subcellular compartmentalization of TGFβ-RII and the dynamics of endosomal formation during the signaling events: An in vivo study on rat mesothelial cells

Interleukin (IL)‐6 modulates transforming growth factor‐β receptor I and II (TGF‐βRI and II) function in epidermal keratinocytes

“…However, it may be that this apparent IL‐6‐mediated shift into the lipid raft is a regulatory mechanism initiated to keep the resulting increase in TGF‐βR expression and further or persistent signalling in check through increased receptor turnover. It was recently shown that TGF‐βRII was detected in EEA‐1‐positive compartments and as inflammation progressed (by day 5), the receptor appeared in caveolin‐1‐positive intracellular structures as well, indicating a potential mechanism to control TGF‐βR activity in inflammatory conditions . Perhaps once receptor expression attains a certain threshold or a particular Smad‐regulated function is required (such as migration), TGF‐βRII is directed into the lipid raft domain ultimately resulting in degradation of the receptor in an attempt to terminate any potential (over) signalling, and this may be represented by peak A in Figure .…”

“…This suggests IL‐6 may modulate TGF‐β activity by trafficking the receptor to the lipid raft portion of the membrane (Figure ). These data support previous findings that a direct interaction occurs between both TGF‐βRI and II, and caveolin. These interactions have functional consequences as evidenced by a significant decrease in Smad2 phosphorylation upon receptor activation (Figures and ).…”

Intracellular trafficking of transforming growth factor β receptors

“…It has been shown that TGFβ receptors located in lipid rafts are internalized through caveolin-dependent pathways [21,[64][65][66] (Fig. 1).…”

Clathrin meets caveolae: fuse or not?

“…The caveolin-1-positive early endosomes may represent the distinct and stale caveolar patches/domains in the limiting membrane of early endosomes, as identified during the endocytic trafficking of the uncoated virus SV40 [3]. Coincidentally, by studying the internalization of TGF-b receptors under in vivo inflammatory conditions, a recent study by another group has also reported the EEA1 and caveolin-1 double-positive vesicular structures [7].…”

“…The physiological significance of the fusion pathway in regulating TGF-b or EGFR signaling is less addressed in this study. However, another recent study has proposed that the fusion of caveolae with the early and late endocytic compartments may help to attenuate the TGF-b signaling under in vivo inflammatory conditions [7]. The discovery of the clathrin-and caveolae-fused pathway will lead to more interesting findings in cell signaling, virus infection [9] and other membrane trafficking-involved events.…”