Glutamylation is a negative regulator of microtubule growth

Chen, Jiayi; Roll-Mecak, Antonina

doi:10.1091/mbc.e23-01-0030

Cited by 8 publications

(2 citation statements)

References 100 publications

(132 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2b). Specifically, EB3 comet elongation in TTLL1 mnKO increased aligning with recent in vitro findings that show augmented microtubule growth rate upon deglutamylation 39 . Concomitant to the increased microtubule mass and reduced PolyE levels, a higher percentage of neuromuscular synapses remained innervated by two or more axons in TTLL1 mnKO vs. control muscles at all postnatal ages tested (Fig.…”

Section: Genetic Ablation Of Ttll1 But Not Of Ttll7 Delays Neuromuscu...supporting

confidence: 88%

Polyglutamylation of microtubules drives neuronal remodeling

Gavoci,

Zhiti,

Rusková

et al. 2024

Preprint

View full text Add to dashboard Cite

Developmental remodeling shapes neural circuits via activity-dependent pruning of synapses and axons. The cytoskeleton is critical for this process, as microtubule loss via enzymatic severing is an early step of pruning across many circuits and species. However, how microtubule-severing enzymes, such as spastin, are activated in specific neuronal compartments remains unknown. Here, we reveal that polyglutamylation, a posttranslational tubulin modification that is enriched in neurons, plays an instructive role in developmental remodeling by tagging microtubules for severing. Motor neuron-specific gene deletion of enzymes that add or remove tubulin polyglutamylation—TTLL glutamylases vs. CCP deglutamylases—accelerates or delays neuromuscular synapse remodeling in a neurotransmission-dependent manner. This mechanism is not specific to peripheral synapses but also operates in central circuits, e.g., the hippocampus. Thus, tubulin polyglutamylation acts as an activity-dependent rheostat of remodeling and shapes neuronal morphology and connectivity.

show abstract

Section: Genetic Ablation Of Ttll1 But Not Of Ttll7 Delays Neuromuscu...supporting

confidence: 88%

Polyglutamylation of microtubules drives neuronal remodeling

Gavoci,

Zhiti,

Rusková

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Polyglutamylation functionalizes the intrinsically disordered C-terminal tails of tubulin that decorate the outside of the microtubule. Glutamylation does not chemically stabilize microtubules directly [60], but this modification is strongly enriched on cellular microtubules that are resistant to temperature and drug-induced depolymerization. Its effects on microtubule mechanics are unknown [6].…”

Section: Resultsmentioning

confidence: 99%

Nonequilibrium bending fluctuations reveal microtubule mechanicsin-vivoand their regulation by glutamylation

Nishi,

Raja,

Pham

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Cells can be described as active composite materials. The mechanical properties of cells are controlled by complex polymer networks and are dynamically tuned for diverse cellular processes driven by force-generating motor proteins. Microtubules are the most rigid protein polymers in the cytoskeleton, and their material properties have been measured in vitro by active bending or by analyzing thermal bending fluctuations. Microtubule mechanics in living cells are extremely difficult to probe directly, while fluctuations are difficult to interpret because they are generated by active forces in a surrounding cytoplasm with poorly understood material properties. Here we introduce a method to measure the elastic properties of microtubules in living cells by making use of motor-generated forces that drive bending fluctuations. Bending dynamics are governed by three main factors: microtubule material properties, cytoskeletal active forces, and the response characteristics of the surrounding cytoplasm. We show theoretically that, when one factor can be independently determined, the other two can be derived from observed fluctuations. Using this method we discovered that polyglutamylation, a post-translational modification enriched on microtubule arrays that need to withstand large mechanical forces such as those in axons or cilia, increases microtubule stiffness in living cells. Our work provides a theoretical and experimental framework to study microtubule mechanics and their regulation by tubulin modifications and microtubule effectors in complex cellular environments. The approach can be extended to other large aspect ratio cellular structures such as the endoplasmic reticulum or the mitochondrial network.

show abstract

γ‐Glutamylation of Isopropylamine by Fermentation

Benninghaus,

Zagami,

Tassini

et al. 2023

ChemBioChem

View full text Add to dashboard Cite

Glutamylation yields N‐functionalized amino acids in several natural pathways. γ‐Glutamylated amino acids may exhibit improved properties for their industrial application, e. g., as taste enhancers or in peptide drugs. γ‐Glutamyl−isopropylamide (GIPA) can be synthesized from isopropylamine (IPA) and l‐glutamate. In Pseudomonas sp. strain KIE171, GIPA is an intermediate in the biosynthesis of l‐alaninol (2‐amino‐1‐propanol), a precursor of the fluorochinolone antibiotic levofloxacin and of the chloroacetanilide herbicide metolachlor. In this study, fermentative production of GIPA with metabolically engineered Pseudomonas putida KT2440 using γ‐glutamylmethylamide synthetase (GMAS) from Methylorubrum extorquens was established. Upon addition of IPA during growth with glycerol as carbon source in shake flasks, the recombinant strain produced up to 21.8 mM GIPA. In fed‐batch bioreactor cultivations, GIPA accumulated to a titer of 11 g L−1 with a product yield of 0.11 g g−1 glycerol and a volumetric productivity of 0.24 g L−1 h−1. To the best of our knowledge, this is the first fermentative production of GIPA.

show abstract

Glutamylation is a negative regulator of microtubule growth

Cited by 8 publications

References 100 publications

Polyglutamylation of microtubules drives neuronal remodeling

Polyglutamylation of microtubules drives neuronal remodeling

Nonequilibrium bending fluctuations reveal microtubule mechanicsin-vivoand their regulation by glutamylation

γ‐Glutamylation of Isopropylamine by Fermentation

Contact Info

Product

Resources

About