Signaling in the crowded cell. (December 2021)

• Record Type: Journal Article
• Authors: Nussinov, Ruth; Tsai, Chung-Jung; Jang, Hyunbum
• Is Part Of: Current opinion in structural biology. Volume 71(2021)
• Page Start: 43
• Page End: 50
• Publication Date: 2021-12
• Subjects: Molecular biology -- Periodicals; 570
• DOI: 10.1016/j.sbi.2021.05.009
• Languages: English
• ISSNs: 0959-440X

Abstract

Abstract: High-resolution technologies have clarified some of the principles underlying cellular actions. However, understanding how cells receive, communicate, and respond to signals is still challenging. Questions include how efficient regulation of assemblies, which execute cell actions at the nanoscales, transmits productively at micrometer scales, especially considering the crowded environment, and how the cell organization makes it happen. Here, we describe how cells can navigate long-range diffusion-controlled signaling via association/dissociation of spatially proximal entities. Dynamic clusters can span the cell, engaging in most signaling steps. Effective local concentration, allostery, scaffolding, affinities, and the chemical and mechanical properties of the macromolecules and the environment play key roles. Signaling strength and duration matter, for example, deciding if a mutation promotes cancer or developmental syndromes. Highlights: How productive cell signaling is executed in the crowded cell is a challenge Cell signaling may need to transduce over large length scales Clustering, affinity, concentration, the endoplasmic reticulum, microtubules, and phase separation are key Chemical and mechanical properties of the macromolecules and the environment matter Signaling strength may decide if mutation is oncogenic or acts in another syndrome