Mechanism of exportin retention in the cell nucleus.
J Cell Biol
; 223(2)2024 02 05.
Article
em En
| MEDLINE
| ID: mdl-38241019
ABSTRACT
Exportin receptors are concentrated in the nucleus to transport essential cargoes out of it. A mislocalization of exportins to the cytoplasm is linked to disease. Hence, it is important to understand how their containment within the nucleus is regulated. Here, we have studied the nuclear efflux of exportin2 (cellular apoptosis susceptibility protein or CAS) that delivers karyopherinα (Kapα or importinα), the cargo adaptor for karyopherinß1 (Kapß1 or importinß1), to the cytoplasm in a Ran guanosine triphosphate (RanGTP)-mediated manner. We show that the N-terminus of CAS attenuates the interaction of RanGTPase activating protein 1 (RanGAP1) with RanGTP to slow GTP hydrolysis, which suppresses CAS nuclear exit at nuclear pore complexes (NPCs). Strikingly, a single phosphomimetic mutation (T18D) at the CAS N-terminus is sufficient to abolish its nuclear retention and coincides with metastatic cellular behavior. Furthermore, downregulating Kapß1 disrupts CAS nuclear retention, which highlights the balance between their respective functions that is essential for maintaining the Kapα transport cycle. Therefore, NPCs play a functional role in selectively partitioning exportins in the cell nucleus.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Núcleo Celular
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Proteína ran de Ligação ao GTP
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Proteína de Suscetibilidade a Apoptose Celular
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Carioferinas
Limite:
Humans
Idioma:
En
Revista:
J Cell Biol
/
J. cell. biol
/
Journal of cell biology
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
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