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ER proteins decipher the tubulin code to regulate organelle distribution

Organelles move along differentially modified microtubules to establish and maintain their proper distributions and functions(1,2). However, how cells interpret these post-translational microtubule modification codes to selectively regulate organelle positioning remains largely unknown. The endoplas...

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Detalles Bibliográficos
Autores principales: Zheng, Pengli, Obara, Christopher J., Szczesna, Ewa, Nixon-Abell, Jonathon, Mahalingan, Kishore K., Roll-Mecak, Antonina, Lippincott-Schwartz, Jennifer, Blackstone, Craig
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8732269/
https://www.ncbi.nlm.nih.gov/pubmed/34912111
http://dx.doi.org/10.1038/s41586-021-04204-9
Descripción
Sumario:Organelles move along differentially modified microtubules to establish and maintain their proper distributions and functions(1,2). However, how cells interpret these post-translational microtubule modification codes to selectively regulate organelle positioning remains largely unknown. The endoplasmic reticulum (ER) is an interconnected network of diverse morphologies that extends promiscuously throughout the cytoplasm(3), forming abundant contacts with other organelles(4). Dysregulation of endoplasmic reticulum morphology is tightly linked to neurologic disorders and cancer(5,6). Here we demonstrate that three membrane-bound endoplasmic reticulum proteins preferentially interact with different microtubule populations, with CLIMP63 binding centrosome microtubules, kinectin (KTN1) binding perinuclear polyglutamylated microtubules, and p180 binding glutamylated microtubules. Knockout of these proteins or manipulation of microtubule populations and glutamylation status results in marked changes in endoplasmic reticulum positioning, leading to similar redistributions of other organelles. During nutrient starvation, cells modulate CLIMP63 protein levels and p180–microtubule binding to bidirectionally move endoplasmic reticulum and lysosomes for proper autophagic responses.