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Abstract
Membraneless granules assemble in different cell types and cellular loci and are the focus of intense research due to their fundamental importance for cellular organization. These dynamic organelles are commonly assembled from RNA and protein components and exhibit soft matter characteristics of molecular condensates currently characterized with biophysical approaches and super-resolution microscopy imaging. In addition, research on the molecular mechanisms of the RNA–protein granules assembly provided insights into the formation of abnormal granules and molecular aggregates, which takes place during many neurodegenerative disorders including Parkinson’s diseases (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). While these disorders are associated with formation of abnormal granules, membraneless organelles are normally assembled in neurons and contribute to translational control and affect stability of neuronal RNAs. More recently, a new subtype of membraneless granules was identified in Drosophila glia (glial granules). Interestingly, glial granules were found to contain proteins which are the principal components of the membraneless granules in germ cells (germ granules), indicating some similarity in the functional assembly of these structures in glia and germline. This mini review highlights recent research on glial granules in the context of other membraneless organelles, including their assembly mechanisms and potential functions in the nervous system.
Highlights
Since description of characteristic membraneless granules in germ cells of over 80 animal species in eight phyla documented several decades ago (Eddy, 1975), it is recognized that the assembly of large intracellular organelles, which lack the membrane, is one of the fundamental landmarks of cellular organization
Some protein components of germ granules assemble into the granules as distinct clusters as well; the proteins show some overlap in the granules
The author highlights novel membraneless granules identified in glia of the adult Drosophila brain (Tindell et al, 2020), which were found to contain protein components of germ granules and discuss the potential significance of glial granules for brain functions in the context of other membraneless organelles
Summary
Since description of characteristic membraneless granules in germ cells of over 80 animal species in eight phyla documented several decades ago (Eddy, 1975), it is recognized that the assembly of large intracellular organelles, which lack the membrane, is one of the fundamental landmarks of cellular organization. Many membraneless structures share landmark molecular characteristics, such as the presence of intrinsically disordered proteins (IDPs) or protein regions (IDPRs), which lack a defined folded structure, and low-complexity regions (LCRs), which may or may not have a distinct structure but show low diversity of their amino acids (Martin and Mittag, 2018) These protein regions are important components that can drive the assembly (condensation) of membraneless granules using their multivalent low-affinity associations with their interacting partners. Of SMN protein, and not its two IDPRs, is sufficient for formation of membraneless condensates (Courchaine et al, 2021) In this mini review, the author highlights novel membraneless granules identified in glia of the adult Drosophila brain (referred to as “glial granules”) (Tindell et al, 2020), which were found to contain protein components of germ granules and discuss the potential significance of glial granules for brain functions in the context of other membraneless organelles
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