bims-fascar Biomed News
on Phase separation and cellular architecture
Issue of 2019‒05‒12
three papers selected by
Victoria Yan
Max Planck Institute of Molecular Cell Biology and Genetics

  1. Trends Cell Biol. 2019 May 07. pii: S0962-8924(19)30074-1. [Epub ahead of print]
    Raff JW.
      There is currently intense interest in the idea that many membraneless organelles might assemble through phase separation of their constituent molecules into biomolecular 'condensates' that have liquid-like properties. This idea is intuitively appealing, especially for complex organelles such as centrosomes, where a liquid-like structure would allow the many constituent molecules to diffuse and interact with one another efficiently. I discuss here recent studies that either support the concept of a liquid-like centrosome or suggest that centrosomes are assembled upon a more solid, stable scaffold. I suggest that it may be difficult to distinguish between these possibilities. I argue that the concept of biomolecular condensates is an important advance in cell biology, with potentially wide-ranging implications, but it seems premature to conclude that centrosomes, and perhaps other membraneless organelles, are necessarily best described as liquid-like phase-separated condensates.
    Keywords:  PCM; biomolecular condensates; cell division; centriole; centrosome; mitosis; phase separation
  2. Biochim Biophys Acta Proteins Proteom. 2019 May 02. pii: S1570-9639(19)30080-9. [Epub ahead of print]
    Nasir I, Onuchic PL, Labra SR, Deniz AA.
      Intrinsically disordered proteins (IDPs) are ubiquitous in proteomes and serve in a range of cellular functions including signaling, regulation, transport and enzyme function. IDP misfunction and aggregation are also associated with several diseases including neurodegenerative diseases and cancer. During the past decade, single-molecule methods have become popular for detailed biophysical and structural studies of these complex proteins. This work has included recent applications to cellular liquid-liquid phase separation (LLPS), relevant for functional dynamics of membraneless organelles such as the nucleolus and stress granules. In this concise review, we cover the conceptual motivations for development and application of single-molecule fluorescence methods for such IDP studies. We follow with a few key examples of systems and biophysical problems that have been addressed, and conclude with thoughts for emerging and future directions.
    Keywords:  Intrinsically disordered proteins; Liquid-liquid phase separation; Single-molecule FRET; Single-molecule biophysics
  3. Cell Mol Life Sci. 2019 May 09.
    Chánez-Paredes S, Montoya-García A, Schnoor M.
      The actin-related protein complex 2/3 (Arp2/3) generates branched actin networks important for many cellular processes such as motility, vesicular trafficking, cytokinesis, and intercellular junction formation and stabilization. Activation of Arp2/3 requires interaction with actin nucleation-promoting factors (NPFs). Regulation of Arp2/3 activity is achieved by endogenous inhibitory proteins through direct binding to Arp2/3 and competition with NPFs or by binding to Arp2/3-induced actin filaments and disassembly of branched actin networks. Arp2/3 inhibition has recently garnered more attention as it has been associated with attenuation of cancer progression, neurotoxic effects during drug abuse, and pathogen invasion of host cells. In this review, we summarize current knowledge on expression, inhibitory mechanisms and function of endogenous proteins able to inhibit Arp2/3 such as coronins, GMFs, PICK1, gadkin, and arpin. Moreover, we discuss cellular consequences of pharmacological Arp2/3 inhibition.
    Keywords:  Actin cytoskeleton; Adhesion; CK666; Cofilin; Cortactin; Endosome; Migration; Vesicle trafficking