Vimentin intermediate filaments stabilize dynamic microtubules by direct interactions

Abstract

The cytoskeleton determines cell mechanics and lies at the heart of important cellular functions. Growing evidence suggests that the manifold tasks of the cytoskeleton rely on the interactions between its filamentous components—actin filaments, intermediate filaments, and microtubules. However, the nature of these interactions and their impact on cytoskeletal dynamics are largely unknown. Here, we show in a reconstituted in vitro system that vimentin intermediate filaments stabilize microtubules against depolymerization and support microtubule rescue. To understand these stabilizing effects, we directly measure the interaction forces between individual microtubules and vimentin filaments. Combined with numerical simulations, our observations provide detailed insight into the physical nature of the interactions and how they affect microtubule dynamics. Thus, we describe an additional, direct mechanism by which cells establish the fundamental cross talk of cytoskeletal components alongside linker proteins. Moreover, we suggest a strategy to estimate the binding energy of tubulin dimers within the microtubule lattice.

Vimentin intermediate filaments organize organellar architecture in response to ER stress

“…Furthermore, previous studies have identified ER organizers such as Kinectin, CLIMP63, p180, VIMP, and the long form of STX5, all of which are associated with the microtubule network (Miyazaki, Wakana et al, 2012, Noda et al, 2014, Ogawa-Goto, Tanaka et al, 2007, Shen, Zheng et al, 2019, Vedrenne, 2005). Previously described interplay between Vimentin and microtubule filaments (Gan et al, 2016, Hookway, Ding et al, 2015, Schaedel, Lorenz et al, 2021) or the actin cytoskeleton (Jiu, Lehtimaki et al, 2015, Serres, Samwer et al, 2020) underscores the complexity inherent in the cell’s cytoskeletal foundation. At the same time, our EM reconstruction of the perinuclear region suggests that different types of connections between the ER and various cytoskeletal elements may occur in parallel while we did not observe intense interaction between IF and microtubules.…”

GFAP splice variants fine-tune glioma cell invasion and tumour dynamics by modulating migration persistence

“…Previous studies have shown that the IF-network can promote migration persistence by modulating microtubule organization and cell polarity [42][43][44] . Whether the absence of GFAPα or dominance of GFAPδ regulates directional migration similarly remains to be elucidated.…”

Intermediate Filaments from Tissue Integrity to Single Molecule Mechanics

“…A recent study on composite networks of vimentin and microtubules has shown that vimentin modifies the stability of the microtubule network by regulating microtubule dynamic instability [113]. Optical trapping reveals strong interactions between a single microtubule and vimentin IF.…”