Spastin regulates VAMP7-containing vesicles trafficking in cortical neurons.


Plaud C1, Joshi V1, Marinello M1, Pastré D1, Galli T2, Curmi PA1, Burgo A3.


Author information

1  Structure and Activity of Normal and Pathological Biomolecules, INSERM U1204, Université d' Evry, France.
2  Inserm URL U950, Institut Jacques Monod, France.
3  Structure and Activity of Normal and Pathological Biomolecules, INSERM U1204, Université d' Evry, France. Electronic address: andrea.burgo@univ-evry.fr.

Abstract

Alteration of axonal transport has emerged as a common precipitating factor in several neurodegenerative disorders including Human Spastic Paraplegia (HSP). Mutations of the SPAST (SPG4) gene coding for the spastin protein account for 40% of all autosomal dominant uncomplicated HSP. By cleaving microtubules, spastin regulates several cellular processes depending on microtubule dynamics including intracellular membrane trafficking. Axonal transport is fundamental for the viability of motor neurons which often have very long axons and thus require efficient communication between the cell body and its periphery. Here we found that the anterograde velocity of VAMP7 vesicles, but not that of VAMP2, two vesicular-SNARE proteins implicated in neuronal development, is enhanced in SPG4-KO neurons. We showed that this effect is associated with a slight increase of the level of acetylated tubulin in SPG4-KO neurons and correlates with an enhanced activity of kinesin-1 motors. Interestingly, we demonstrated that an artificial increase of acetylated tubulin by drugs reproduces the effect of Spastin KO on VAMP7 axonal dynamics but also increased its retrograde velocity. Finally, we investigated the effect of microtubule targeting agents which rescue axonal swellings, on VAMP7 and microtubule dynamics. Our results suggest that microtubule stabilizing agents, such as taxol, may prevent the morphological defects observed in SPG4-KO neurons no simply rescuing the altered anterograde transport to basal levels but rather by increasing the retrograde velocity of axonal cargoes.

This part of the website could either be in French or English, depending on the sources of the actualities.

Autres Publications

 28 mai 2019
Kremen1-induced cell death is regulated by homo- and heterodimerization
 20 mai 2019
Impaired attentional modulation of sensorimotor control and cortical excitability in schizophrenia
 06 mai 2019
Routing Hippocampal Information Flow through Parvalbumin Interneuron Plasticity in Area CA2
 30 avril 2019
Individual recovery profiles of manual dexterity, and relation to corticospinal lesion load and excitability after stroke —a longitudinal pilot study
 11 avril 2019
Neuronal activity in vivo enhances functional myelin repair
 10 avril 2019
Somatostatin Serves a Modulatory Role in the Mouse Olfactory Bulb: Neuroanatomical and Behavioral Evidence
 13 février 2019
A new painkiller nanomedicine to bypass the blood-brain barrier and the use of morphine
 11 février 2019
Live Tracking of Inter-organ Communication by Endogenous Exosomes In Vivo
 06 février 2019
Mitochondria, Metabolism, and Redox Mechanisms in Psychiatric Disorders
 09 janvier 2019
In vivo Optogenetic Approach to Study Neuron-Oligodendroglia Interactions in Mouse Pups
 21 décembre 2018
Predictive Modulation of Corticospinal Excitability and Implicit Encoding of Movement Probability in Schizophrenia
 07 novembre 2018
Manual Dexterity and Aging: A Pilot Study Disentangling Sensorimotor From Cognitive Decline
 05 novembre 2018
Burnout in medical students before residency: A systematic review and meta-analysis
 03 octobre 2018
Tobacco Smoking and Psychotic-Like Experiences in a General Population Sample
 14 juin 2018
The GABAergic Gudden's dorsal tegmental nucleus: A new relay for serotonergic regulation of sleep-wake behavior in the mouse
 07 juin 2018
a2- and b2-Adrenoreceptor-Mediated Efficacy of the Atypical Antidepressant Agomelatine Combined With Gabapentin to Suppress Allodynia in Neuropathic Rats With Ligated Infraorbital or Sciatic Nerve
 18 mai 2018
Memory circuits: CA2
 07 mai 2018
Cortical developmental death: selected to survive or fated to die
 05 avril 2018
Plasma amyloid levels within the Alzheimer’s process and correlations with central biomarkers
 02 mars 2018
Longitudinal Analyses of Blood Transcriptome During Conversion to Psychosis.