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LAT1 supports mitotic progression through Golgi unlinking in an amino acid transport activity-independent manner.
Yanagida, Sakura; Yuki, Ryuzaburo; Saito, Youhei; Nakayama, Yuji.
Afiliación
  • Yanagida S; Laboratory of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto, Japan.
  • Yuki R; Laboratory of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto, Japan. Electronic address: yuki2019@mb.kyoto-phu.ac.jp.
  • Saito Y; Laboratory of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto, Japan.
  • Nakayama Y; Laboratory of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto, Japan. Electronic address: nakayama@mb.kyoto-phu.ac.jp.
J Biol Chem ; 300(10): 107761, 2024 Oct.
Article en En | MEDLINE | ID: mdl-39270820
ABSTRACT
Amino acid transporters play a vital role in cellular homeostasis by maintaining protein synthesis. L-type amino acid transporter 1 (LAT1/SLC7A5/CD98lc) is a major transporter of large neutral amino acids in cancer cells because of its predominant expression. Although amino acid restriction with various amino acid analog treatments is known to induce mitotic defects, the involvement of amino acid transporters in cell division remains unclear. In this study, we identified that LAT1 is responsible for mitotic progression in a transport activity-independent manner. LAT1 knockdown activates the spindle assembly checkpoint, leading to a delay in metaphase. LAT1 maintains proper spindle orientation with confinement of the lateral cortex localization of the NuMA protein, which mediates the pulling force against the mitotic spindle toward the lateral cortex. Unexpectedly, JPH203, an inhibitor of LAT1 amino acid transport activity, does not affect mitotic progression. Moreover, the transport activity-deficient LAT1 mutant maintains the proper spindle orientation and mitotic progression. LAT1 forms a heterodimer with CD98 (SLC3A2/CD98hc) both in interphase and mitosis. Although CD98 knockdown decreases the plasma membrane localization of LAT1, it does not affect mitotic progression. LAT1 is localized to the Golgi and ER not only at the plasma membrane in interphase, and promotes Golgi unlinking during the mitotic entry, leading to centrosome maturation. These results suggest that LAT1 supports mitotic progression in an amino acid transport activity-independent manner and that Golgi-localized LAT1 is important for mitotic progression through the acceleration of Golgi unlinking and centrosome maturation. These findings reveal a novel LAT1 function in mitosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transportador de Aminoácidos Neutros Grandes 1 / Aparato de Golgi / Mitosis / Huso Acromático Límite: Humans Idioma: En Revista: J Biol Chem Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transportador de Aminoácidos Neutros Grandes 1 / Aparato de Golgi / Mitosis / Huso Acromático Límite: Humans Idioma: En Revista: J Biol Chem Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos