美国国立卫生研究院Craig Blackstone、Pengli Zheng等研究人员合作发现，内质网蛋白破译管蛋白编码来调节细胞器分布。相关论文于2021年12月15日在线发表在《自然》杂志上。

研究人员发现，三种膜结合的内质网蛋白优先与不同的微管群相互作用，CLIMP63结合中心体微管，Kinectin（KTN1）结合核周围多谷氨酸化微管，p180结合谷氨酸化微管。敲除这些蛋白或操纵微管的数量和谷氨酸化状态会导致内质网定位的明显变化，从而导致其他细胞器的类似重新分布。在营养饥饿期间，细胞调节CLIMP63蛋白水平和p180-微管结合，双向移动内质网和溶酶体，从而作出适当的自噬反应。

据悉，细胞器沿着不同修饰的微管移动，从而建立和维持其适当的分布和功能。然而，细胞如何解释这些翻译后的微管修饰编码以选择性地调节细胞器的定位，在很大程度上仍然是未知的。内质网是一个具有不同形态的互联网络，在整个细胞质中乱七八糟地延伸，与其他细胞器形成大量接触。内质网形态失调与神经系统疾病和癌症有密切联系。

附：英文原文

Title: ER proteins decipher the tubulin code to regulate organelle distribution

Author: Zheng, Pengli, Obara, Christopher J., Szczesna, Ewa, Nixon-Abell, Jonathon, Mahalingan, Kishore K., Roll-Mecak, Antonina, Lippincott-Schwartz, Jennifer, Blackstone, Craig

Issue&Volume: 2021-12-15

Abstract: Organelles move along differentially modified microtubules to establish and maintain their proper distributions and functions1,2. 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 cytoplasm3, forming abundant contacts with other organelles4. Dysregulation of endoplasmic reticulum morphology is tightly linked to neurologic disorders and cancer5,6. 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.

DOI: 10.1038/s41586-021-04204-9

Source: https://www.nature.com/articles/s41586-021-04204-9