Biology subjects

Martino, F.

Publications and source records attributed to Martino, F..

3 recordsLinked to original sources

bioRxiv2023

The Tubulin Nano-Code: a protofilament-specific pattern of tubulin post-translational modifications regulates ciliary beating mechanics

Control of ciliary beating is crucial for motility and signaling in eukaryotic cells and requires spatially restricted interactions between axonemal proteins and specific protofilaments within the ciliary microtubules. How these interactions are regulated remains poorly understood, but increasing evidence indicates that tubulin post-translational modifications (tPTMs) are required for proper ciliary motility. The Tubulin Code refers to the concept that tPTMs can modulate the function of individual microtubules in cells. Here we use a combination of immuno-cryo-electron tomography, expansion microscopy and mutant analysis to show that, in motile cilia, tubulin glycylation and polyglutamylation form mutually exclusive protofilament-specific nano-patterns at sub-microtubular scale. We show that these two nano-patterns are consistent with the distributions of axonemal dyneins and nexin-dynein regulatory complexes, respectively, and are required for their regulation during ciliary beating. Our discovery of a tubulin nano-code in cilia highlights the need of higher-resolution studies also in other cellular compartments to understand the molecular role of tPTMs. One-Sentence SummaryTubulin post-translational modifications form nanopatterns at sub-microtubular scale that enable individual protofilaments to perform specific functions Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/546853v1_ufig1.gif" ALT="Figure 1"> View larger version (62K): org.highwire.dtl.DTLVardef@253704org.highwire.dtl.DTLVardef@13f0a8forg.highwire.dtl.DTLVardef@1ce673dorg.highwire.dtl.DTLVardef@1dc04e1_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2021

The mechanical regulation of RNA binding protein hnRNPC in the failing heart

Cardiac pathologies are characterized by intense remodeling of the extracellular matrix (ECM) that eventually leads to heart failure. Cardiomyocytes respond to the ensuing biomechanical stress by re-expressing fetal contractile proteins via transcriptional and post-transcriptional processes, like alternative splicing (AS). Here, we demonstrate that the heterogeneous nuclear ribonucleoprotein C (hnRNPC) is upregulated and relocates to the sarcomeric Z-disk upon ECM pathological remodeling. We show that this is an active site of localized translation, where the ribonucleoprotein associates to the translation machinery. Alterations in hnRNPC expression and localization can be mechanically determined and affect the AS of numerous mRNAs involved in mechanotransduction and cardiovascular diseases, like Hippo pathway effector YAP1. We propose that cardiac ECM remodeling serves as a switch in RNA metabolism by impacting an associated regulatory protein of the spliceosome apparatus. These findings offer new insights on the mechanism of mRNAs homeostasis mechanoregulation in pathological conditions.

pathology↗

bioRxiv2019

Microtubule Nucleation by Single Human γTuRC in a Partly Open Asymmetric Conformation

The {gamma}-tubulin ring complex ({gamma}TuRC) is the major microtubule nucleator in cells. However, the mechanism of its regulation is not understood. Here, we purified human {gamma}TuRC and quantitatively characterized its nucleation properties in a TIRF microscopy-based real-time nucleation assay. We find that microtubule nucleation by {gamma}TuRC is kinetically inhibited compared to microtubule elongation. Determining the cryo-EM structure of {gamma}TuRC at 4 [A] resolution reveals an asymmetric conformation with only part of the complex in a closed conformation matching the microtubule geometry. Several factors stabilise the closed conformation. One is actin in the core of the complex and others, likely MZT1 or MZT2, line the outer perimeter of the closed part of {gamma}TuRC. The opposed side of {gamma}TuRC is in an open, nucleation-incompetent conformation, leading to a structural asymmetry, explaining the kinetic inhibition of nucleation by human {gamma}TuRC. Our data suggest possible regulatory mechanisms for microtubule nucleation by {gamma}TuRC closure.

biochemistry↗