Invited review: Microtubule severing enzymes couple atpase activity with tubulin GTPase spring loading

Bailey, Megan E.; Jiang, Nan; Dima, Ruxandra I.; Ross, Jennifer L.

doi:10.1002/bip.22842

Cited by 25 publications

(52 citation statements)

References 109 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There have been a number of studies that have catalogued the effects of individual types of MAPs on microtubule dynamics. 37–40 …”

Section: Feedback and Control In The Assembly Of Tubulin Into Microtumentioning

confidence: 99%

“…These proteins are evolutionarily distinct from kinesin enzymes. 40, 59 They are from the ATPases Associated with various cellular activities (AAA+) enzyme family – an ancient enzyme family with members in all cell types and organisms. The AAA+ enzymes form hexameric rings with an active pore in the middle.…”

Section: Feedback and Control In The Assembly Of Tubulin Into Microtumentioning

confidence: 99%

See 1 more Smart Citation

Non-equilibrium assembly of microtubules: from molecules to autonomous chemical robots

2017

Self Cite

View full text Add to dashboard Cite

Biological systems have evolved to harness non-equilibrium processes from the molecular to the macro scale. It is currently a grand challenge of chemistry, materials science, and engineering to understand and mimic biological systems that have the ability to autonomously sense stimuli, process these inputs, and respond by performing mechanical work. New chemical systems are responding to the challenge and form the basis for future responsive, adaptive, and active materials. In this article, we describe a particular biochemical-biomechanical network based on the microtubule cytoskeletal filament – itself a non-equilibrium chemical system. We trace the non-equilibrium aspects of the system from molecules to networks and describe how the cell uses this system to perform active work in essential processes. Finally, we discuss how microtubule-based engineered systems can serve as testbeds for autonomous chemical robots composed of biological and synthetic components.

show abstract

“…There have been a number of studies that have catalogued the effects of individual types of MAPs on microtubule dynamics. 37–40 …”

Section: Feedback and Control In The Assembly Of Tubulin Into Microtumentioning

confidence: 99%

Section: Feedback and Control In The Assembly Of Tubulin Into Microtumentioning

confidence: 99%

Non-equilibrium assembly of microtubules: from molecules to autonomous chemical robots

2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, tubulin heterodimers are only able to hydrolyze the GTP bound to beta-tubulin and this hydrolysis changes the conformation of tubulin dimer-dimer interaction (i.e., the conformation of the protofilaments that make up microtubules). GTP-bound tubulin dimers tend to orient the microtubule in a straight conformation, whereas GDP-tubulin bends the lattice and “spring loads” the microtubule with potential energy that favors catastrophe, which is an explosive bout of disassembly (30). The hydrolysis of GTP-beta-tubulin to GDP-beta-tubulin only happens after the free tubulin has assembled into the microtubule.…”

Section: Microtubule Dynamics and Stability In Neuronsmentioning

confidence: 99%

Microtubules in health and degenerative disease of the nervous system

Matamoros

Baas

2016

Brain Research Bulletin

112

View full text Add to dashboard Cite

Microtubules are essential for the development and maintenance of axons and dendrites throughout the life of the neuron, and are vulnerable to degradation and disorganization in a variety of neurodegenerative diseases. Microtubules, polymers of tubulin heterodimers, are intrinsically polar structures with a plus end favored for assembly and disassembly and a minus end less favored for these dynamics. In the axon, microtubules are nearly uniformly oriented with plus ends out, whereas in dendrites, microtubules have mixed orientations. Microtubules in developing neurons typically have a stable domain toward the minus end and a labile domain toward the plus end. This domain structure becomes more complex during neuronal maturation when especially stable patches of polyaminated tubulin become more prominent within the microtubule. Microtubules are the substrates for molecular motor proteins that transport cargoes toward the plus or minus end of the microtubule, with motor-driven forces also responsible for organizing microtubules into their distinctive polarity patterns in axons and dendrites. A vast array of microtubule-regulatory proteins impart direct and indirect changes upon the microtubule arrays of the neuron, and these include microtubule-severing proteins as well as proteins responsible for the stability properties of the microtubules. During neurodegenerative diseases, microtubule mass is commonly diminished, and the potential exists for corruption of the microtubule polarity patterns and microtubule-mediated transport. These ill effects may be a primary causative factor in the disease or may be secondary effects, but regardless, therapeutics capable of correcting these microtubule abnormalities have great potential to improve the status of the degenerating nervous system.

show abstract

“…Spastin is the most well‐studied microtubule‐severing enzyme . However, despite its important biological functions and physiological implications, its working mechanism is still far from clear.…”

Section: Discussionmentioning

confidence: 99%

The AAA protein spastin possesses two levels of basal ATPase activity

et al. 2018

View full text Add to dashboard Cite

The AAA ATPase spastin is a microtubule-severing enzyme that plays important roles in various cellular events including axon regeneration. Herein, we found that the basal ATPase activity of spastin is negatively regulated by spastin concentration. By determining a spastin crystal structure, we demonstrate the necessity of intersubunit interactions between spastin AAA domains. Neutralization of the positive charges in the microtubule-binding domain (MTBD) of spastin dramatically decreases the ATPase activity at low concentration, although the ATP-hydrolyzing potential is not affected. These results demonstrate that, in addition to the AAA domain, the MTBD region of spastin is also involved in regulating ATPase activity, making interactions between spastin protomers more complicated than expected.

show abstract

Invited review: Microtubule severing enzymes couple atpase activity with tubulin GTPase spring loading

Cited by 25 publications

References 109 publications

Non-equilibrium assembly of microtubules: from molecules to autonomous chemical robots

Non-equilibrium assembly of microtubules: from molecules to autonomous chemical robots

Microtubules in health and degenerative disease of the nervous system

The AAA protein spastin possesses two levels of basal ATPase activity

Contact Info

Product

Resources

About