Amyloid-like Self-Assembly of a Cellular Compartment

Abstract

SUMMARY Most vertebrate oocytes contain a Balbiani body; a large, non-membrane bound compartment packed with RNA, mitochondria and other organelles. Little is known about this compartment, though it specifies germ-line identity in many non-mammalian vertebrates. We show Xvelo, a disordered protein with an N-terminal prion-like domain, is an abundant constituent of Xenopus Balbiani bodies. Disruption of the prion-like domain of Xvelo, or substitution with a prion-like domain from an unrelated protein interferes with its incorporation into Balbiani bodies in vivo. Recombinant Xvelo forms amyloid-like networks in vitro. Amyloid-like assemblies of Xvelo recruit both RNA and mitochondria in binding assays. We propose that Xenopus Balbiani bodies form by amyloid-like assembly of Xvelo, accompanied by co-recruitment of mitochondria and RNA. Prion-like domains are found in germ plasm organizing proteins in other species, suggesting that Balbiani body formation by amyloid-like assembly could be a conserved mechanism that helps oocytes function as long-lived germ cells.

Phosphorylation of the FUS low‐complexity domain disrupts phase separation, aggregation, and toxicity

“…Recent work strongly points to the ability of these domains to form functional interactions with specific sets of proteins bearing similar low‐complexity (or prion‐like) domains (Kato et al , 2012; Molliex et al , 2015). Currently, many questions remain about the molecular nature of these interactions inside RNP granules—that is, where each specific membraneless organelle falls on a continuum of molecular architectures (Aguzzi & Altmeyer, 2016) ranging from structured cross‐β amyloids to disordered polymer chains (Patel et al , 2015; Xiang et al , 2015; Boke et al , 2016). However, it is clear that low‐complexity domains specify and mediate functional protein–protein interactions and pathological self‐aggregation.…”

Why the way we look at things in reproductive medicine is changing

“…So why the big deal about the BB? As luck would have it, although from a different animal model system, the BB seems to be held together by a class of proteins resembling amyloid, the distinctive components of tangles that are believed to be causative in the progression of certain age-related neurological diseases [5].…”

The balbiani body and the concept of physiological amyloids

“…Here, we discuss our recent work showing how physiological amyloids can be involved in preserving dormancy in vertebrate oocytes, by forming a subcellular compartment, called the Balbiani body. 5 The Balbiani body is a non-membrane bound compartment packed with mitochondria, E.R, Golgi, and RNA. 5 It is present in the cytoplasm of all vertebrate oocytes in which it has been looked for.…”

“…5 The Balbiani body is a non-membrane bound compartment packed with mitochondria, E.R, Golgi, and RNA. 5 It is present in the cytoplasm of all vertebrate oocytes in which it has been looked for. The Balbiani body is a transient structure, as it only exists in the dormant oocytes, and disperses once the oocyte is activated.…”

“…We concluded that Xvelo self-assembly drives the Balbiani body formation and an Xvelo matrix is the glue that keeps the components of Balbiani body together. 5 How can a protein form a stable, micron-scale, organelle embedding matrix in the cytoplasm? The answer proved to be an unexpected link between oocyte biology and amyloid and prion concepts.…”