Different routes of bone morphogenic protein (BMP) receptor endocytosis influence BMP signaling.
Mol Cell Biol
; 26(20): 7791-805, 2006 Oct.
Article
in En
| MEDLINE
| ID: mdl-16923969
ABSTRACT
Endocytosis is important for a variety of functions in eukaryotic cells, including the regulation of signaling cascades via transmembrane receptors. The internalization of bone morphogenetic protein (BMP) receptor type I (BRI) and type II (BRII) and its relation to signaling were largely unexplored. Here, we demonstrate that both receptor types undergo constitutive endocytosis via clathrin-coated pits (CCPs) but that only BRII undergoes also caveola-like internalization. Using several complementary approaches, we could show that (i) BMP-2-mediated Smad1/5 phosphorylation occurs at the plasma membrane in nonraft regions, (ii) continuation of Smad signaling resulting in a transcriptional response requires endocytosis via the clathrin-mediated route, and (iii) BMP signaling leading to alkaline phosphatase induction initiates from receptors that fractionate into cholesterol-enriched, detergent-resistant membranes. Furthermore, we show that BRII interacts with Eps15R, a constitutive component of CCPs, and with caveolin-1, the marker protein of caveolae. Taken together, the localization of BMP receptors in distinct membrane domains is prerequisite to their taking different endocytosis routes with specific impacts on Smad-dependent and Smad-independent signaling cascades.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Bone Morphogenetic Proteins
/
Endocytosis
/
Bone Morphogenetic Protein Receptors, Type I
/
Bone Morphogenetic Protein Receptors, Type II
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Cell Biol
Year:
2006
Document type:
Article
Affiliation country:
Germany