Inverting the Topology of a Transmembrane Protein by Regulating the Translocation of the First Transmembrane Helix.
Mol Cell
; 63(4): 567-578, 2016 08 18.
Article
em En
| MEDLINE
| ID: mdl-27499293
ABSTRACT
TM4SF20 (transmembrane 4 L6 family 20) is a polytopic membrane protein that inhibits proteolytic processing of CREB3L1 (cAMP response element-binding protein 3-like 1), a membrane-bound transcription factor that blocks cell division and activates collagen synthesis. Here we report that ceramide stimulates CREB3L1 cleavage by inverting the orientation of TM4SF20 in membranes. In the absence of ceramide, the N terminus of the first transmembrane helix of TM4SF20 is inserted into the endoplasmic reticulum (ER) lumen. This translocation requires TRAM2 (translocating chain-associated membrane protein 2), a membrane protein containing a putative ceramide-interacting domain. In the presence of ceramide, the N terminus of the first transmembrane domain of TM4SF20 is exposed to cytosol. Consequently, the membrane topology of TM4SF20 is inverted, and this form of TM4SF20 stimulates CREB3L1 cleavage. In the presence of ceramide, translocation of TM4SF20 is TRAM2-independent. We designate this mechanism-causing regulated inversion of the membrane topology as "regulated alternative translocation."
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Ceramidas
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Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
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Retículo Endoplasmático
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Tetraspaninas
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Membranas Intracelulares
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Proteínas do Tecido Nervoso
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article