Biology subjects

Renganathan, B.

Publications and source records attributed to Renganathan, B..

3 recordsLinked to original sources

bioRxiv2026

Mitochondria-Coupled Hitchhiking Drives Vimentin Intermediate Filament Transport

Vimentin intermediate filaments (VIFs) undergo active microtubule-dependent transport throughout the cell, with trajectories resembling those of motor-driven organelles, yet our recent work showed that only a small subset of VIFs lies close to microtubules. How VIFs engage the microtubule-based transport machinery, and whether additional transport routes contribute, remain unresolved. We hypothesized that VIFs move indirectly, by hitchhiking on motile organelles, and tested this using mitochondria. Live imaging showed mitochondria and adjacent VIFs moving together, and volume electron microscopy revealed VIFs closely following mitochondrial surfaces at sites distinct from microtubule contacts. Depleting the mitochondrial motor adaptor TRAK1 to inhibit anterograde mitochondrial transport shifted both mitochondria and VIFs toward the nucleus. Driving mitochondria toward the cell periphery with a tailless kinesin-1 in cells lacking endogenous kinesin-1, or toward the cell center with a minus-end-directed motor, redistributed a subset of VIFs in the same direction. Thus, VIF transport to a large extend is accomplished by hitchhiking on motile mitochondria.

cell biology↗

bioRxiv2024

Transport and Organization of Individual Vimentin Filaments Within Dense Networks Revealed by Single Particle Tracking and 3D FIB-SEM

Vimentin intermediate filaments (VIFs) form complex, tight-packed networks; due to this density, traditional ensemble labeling and imaging approaches cannot accurately discern single filament behavior. To address this, we introduce a sparse vimentin-SunTag labeling strategy to unambiguously visualize individual filament dynamics. This technique confirmed known long-range dynein and kinesin transport of peripheral VIFs and uncovered extensive bidirectional VIF motion within the perinuclear vimentin network, a region we had thought too densely bundled to permit such motility. To examine the nanoscale organization of perinuclear vimentin, we acquired high-resolution electron microscopy volumes of a vitreously frozen cell and reconstructed VIFs and microtubules within a [~]50 {micro}m3 window. Of 583 VIFs identified, most were integrated into long, semi-coherent bundles that fluctuated in width and filament packing density. Unexpectedly, VIFs displayed minimal local co-alignment with microtubules, save for sporadic cross-over sites that we predict facilitate cytoskeletal crosstalk. Overall, this work demonstrates single VIF dynamics and organization in the cellular milieu for the first time SummarySingle-particle tracking demonstrates that individual filaments in bundles of vimentin intermediate filaments are transported in the cytoplasm by motor proteins along microtubules. Furthermore, using 3D FIB-SEM the authors showed that vimentin filament bundles are loosely packed and co-aligned with microtubules.

cell biology↗

bioRxiv2022

Gigaxonin is required for intermediate filament transport

Gigaxonin is an adaptor protein for E3 ubiquitin ligase substrates. It is necessary for ubiquitination and degradation of intermediate filament (IF) proteins. Giant axonal neuropathy is a pathological condition caused by mutations in the GAN gene that encodes gigaxonin. This condition is characterized by abnormal accumulation of IFs in both neuronal and non-neuronal cells; however, it is unclear what causes IF aggregation. In this work, we studied the dynamics of IFs using their subunits tagged with a photoconvertible protein mEOS 3.2. We have demonstrated that the loss of gigaxonin dramatically inhibited transport of IFs along microtubules by the microtubule motor kinesin-1. This inhibition was specific for IFs, as other kinesin-1 cargoes, with the exception of mitochondria, were transported normally. Another effect of gigaxonin loss was a more than 20-fold increase in the amount of soluble vimentin oligomers in the cytoplasm of gigaxonin knock-out cells. We speculate that these oligomers saturate a yet unidentified adapter that is required for kinesin-1 binding to IFs, which might inhibit IF transport along microtubules causing their abnormal accumulation.

cell biology↗