Molecular underpinnings of cytoskeletal cross-talk.

Abstract:

:Cross-talk between the microtubule and actin networks has come under intense scrutiny following the realization that it is crucial for numerous essential processes, ranging from cytokinesis to cell migration. It is becoming increasingly clear that proteins long-considered highly specific for one or the other cytoskeletal system do, in fact, make use of both filament types. How this functional duality of "shared proteins" has evolved and how their coadaptation enables cross-talk at the molecular level remain largely unknown. We previously discovered that the mammalian adaptor protein melanophilin of the actin-associated myosin motor is one such "shared protein," which also interacts with microtubules in vitro. In a hypothesis-driven in vitro and in silico approach, we turn to early and lower vertebrates and ask two fundamental questions. First, is the capability of interacting with microtubules and actin filaments unique to mammalian melanophilin or did it evolve over time? Second, what is the functional consequence of being able to interact with both filament types at the cellular level? We describe the emergence of a protein domain that confers the capability of interacting with both filament types onto melanophilin. Strikingly, our computational modeling demonstrates that the regulatory power of this domain on the microscopic scale alone is sufficient to recapitulate previously observed behavior of pigment organelles in amphibian melanophores. Collectively, our dissection provides a molecular framework for explaining the underpinnings of functional cross-talk and its potential to orchestrate the cell-wide redistribution of organelles on the cytoskeleton.

authors

Oberhofer A,Reithmann E,Spieler P,Stepp WL,Zimmermann D,Schmid B,Frey E,Ökten Z

doi

10.1073/pnas.1917964117

subject

Has Abstract

pub_date

2020-02-25 00:00:00

pages

3944-3952

issue

8

eissn

0027-8424

issn

1091-6490

pii

1917964117

journal_volume

117

pub_type

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