The endoplasmic reticulum (ER) is a large, single-copy, membrane-bound organelle that comprises an elaborate 3D network of structurally diverse subdomains: highly curved tubules, flat sheets, and parts that form contacts with nearly every other organelle of the cell. The ER is essential for the synthesis, modification, and transport of membrane and secretory proteins; it is also the site of cytosolic calcium level regulation and synthesis and transport of several lipids. To accommodate the vast range of functions, the ER network spreads throughout the cell, and its functions are distributed into structural subdomains according to their specific requirements. Many structural determinants of the network formation and maintenance have been described; however, it is not yet understood e.g. how different functions are distributed to the various subdomains, why the ER is constantly rearranging its architecture, and how the sheet/tubule –balance is maintained.
Proper ER operation requires an intricate balance within and in-between dynamics, morphology, and functions. While ER structure is in constant flux, it does not move en masse, and the network movement is achieved through dynamics of individual subdomains and through network remodelling, which are accomplished through interactions with the cytoskeleton. Combining live cell imaging, thin section TEM and two 3D-EM methods, we show that dynamic microtubules and actin filament arrays together contribute to the maintenance of ER sheet-tubule balance. Perturbations of microtubule or actin cytoskeleton readily shift the balance towards tubules or sheets, which in turn can result in formation of sheet remnants or long and less fenestrated abnormal sheets. We recently identified the unconventional motor protein myosin 1c localizing to and regulating the ER associated actin filament arrays. Manipulation of myo1c levels disturbed the dynamics of actin arrays and affected ER sheet morphology similarly to actin manipulations with drugs. Tubular ER phenotype of myo1c-depleted cells could be rescued with wild type myo1c, but not with a mutated form lacking the actin binding domain. We propose that ER -associated actin filaments have a role in maintaining the ER sheet-tubule balance and sheet structure by regulating sheet remodeling events, and thus support the maintenance of sheets as a stationary subdomain of the otherwise dynamic ER network.
Knowledge of the mechanisms behind the structural maintenance and dynamics will be the key towards deeper understanding of ER functions and their regulation, and eventually, in unravelling molecular mechanisms behind various ER-associated diseases.
To cite this abstract:Merja Joensuu, Ilya Belevich, Helena Vihinen, Darshan Kumar, Olli Rämö, Behnam Lak, Eija Jokitalo; Structure and dynamics of the endoplasmic reticulum in cultured mammalian cells. The 16th European Microscopy Congress, Lyon, France. https://emc-proceedings.com/abstract/structure-and-dynamics-of-the-endoplasmic-reticulum-in-cultured-mammalian-cells/. Accessed: January 29, 2023
EMC Abstracts - https://emc-proceedings.com/abstract/structure-and-dynamics-of-the-endoplasmic-reticulum-in-cultured-mammalian-cells/