БИОХИМИЯ, 2019, том 84, вып. 12, с. 1839–1853

Регулярные статьи

УДК 576.36; 576.32.36

Феномен фрагментации аппарата Гольджи: почему структура этой органеллы так важна?

Обзор

© 2019 A. Петросян 1,2,3

Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA; E-mail: apetrosyan@unmc.edu

The Nebraska Center for Integrated Biomolecular Communication, Lincoln, NE, USA

The Fred and Pamela Buffett Cancer Center, Omaha, NE, USA

Поступила в редакцию 26.05.2019
После доработки 10.07.2019
Принята к публикации 16.08.2019

DOI: 10.1134/S032097251912008X

КЛЮЧЕВЫЕ СЛОВА: морфология Гольджи, гольджины, джиантин, GM130, GRASP65, резидентные энзимы Гольджи, ЭР-стресс.

Аннотация

Аппарат Гольджи является динамичной органеллой, которая расположена в еринуклеарной области и играет ключевую роль в регуляции клеточного гомеостаза. В то время как посттрансляционная модификация белков обеспечивается резидентными ферментами Гольджи (гликозилтрансферазы, гликозидазы и киназы), лентообразная структура Гольджи и его способность образовывать стопку дискообразных цистерн во многом определяются матриксными белками гольджинами. Среди них джиантин, GM130 и GRASP65 являются уникальными, поскольку формируют тройной комплекс, обеспечивающий стыковку на поверхности Гольджи везикул, движущихся из эндоплазматического ретикулума (ЭР). Гольджи подвергается структурной дезорганизации при ряде патологий, которые объединяет нарушение транспортного сообщения между ЭР и Гольджи: рак, различные неврологические заболевания, включая болезни Альцгеймера, Паркинсона и эпилепсию, алкогольные заболевания печени, ишемический стресс и вирусные инфекции. Гольджи также дезорганизуется во время митоза и апоптоза. В данном обзоре мы анализируем результаты работ, которые демонстрируют, что фрагментация Гольджи приводит не только к избирательной потере резидентных ферментов, но также и к переходу некоторых белков из цитоплазмы в Гольджи. Мы предлагаем новую концепцию, постулирующую, что стрессы ЭР и Гольджи разрушают стыковочный сайт джиантина, но не оказывают существенного влияния на комплекс GM130–GRASP65, тем самым вызывая переход джиантин-зависимых ферментов из Гольджи в цитоплазму. Это приводит к значительным изменениям в постсинтетической модификации белков: отныне процессинг карго во многом определяется вкладом GM130–GRASP65-зависимых ферментов, которые остаются в Гольджи, несмотря на его дезорганизацию. Немалую роль играют и «гостевые» ферменты, которых в норме нет в Гольджи, но из-за отсутствия джиантина они оказываются способны к стыковке на мембранах Гольджи. Индуцированное нарушение цитоскелета также вызывает фрагментацию Гольджи, но не приводит ни к нарушению структуры гольджинов, ни к блокировке внутриклеточной транспортировки.

Финансирование

Работы автора, цитируемые в данном обзоре, поддержаны грантами National Institute of Health (США): K01AA022979-05, P20-GM113126 и 1R01AA027242-01A1.

Конфликт интересов

Автор заявляет, что данное исследование проводилось в отсутствие каких-либо коммерческих или финансовых отношений, которые могли бы быть истолкованы как потенциальный конфликт интересов.

Соблюдение этических норм

Настоящая статья не содержит описания выполненных автором исследований с участием людей и использованием животных в качестве объектов.

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