The extracellular linker of pro-neuregulin-alpha2c is required for efficient sorting and juxtacrine function.
Mol Biol Cell
; 18(2): 380-93, 2007 Feb.
Article
en En
| MEDLINE
| ID: mdl-17108327
ABSTRACT
The neuregulins (NRGs) play important roles in animal physiology, and their disregulation has been linked to diseases such as cancer or schizophrenia. The NRGs may be produced as transmembrane proteins (proNRGs), even though they lack an N-terminal signal sequence. This raises the question of how NRGs are sorted to the plasma membrane. It is also unclear whether in their transmembrane state, the NRGs are biologically active. During studies aimed at solving these questions, we found that deletion of the extracellular juxtamembrane region termed the linker, decreased cell surface exposure of the mutant proNRG(DeltaLinker), and caused its entrapment at the cis-Golgi. We also found that cell surface-exposed transmembrane NRG forms retain biological activity. Thus, a mutant whose cleavage is impaired but is correctly sorted to the plasma membrane activated ErbB receptors in trans and also stimulated proliferation. Because the linker is implicated in surface sorting and the regulation of the cleavage of transmembrane NRGs, our data indicate that this region exerts multiple important roles in the physiology of NRGs.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Señales de Clasificación de Proteína
/
Membrana Celular
/
Neurregulina-1
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Biol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2007
Tipo del documento:
Article
País de afiliación:
España