Rab-dependent cellular trafficking and amyotrophic lateral sclerosis

S. Parakh, E. R. Perri, C. J. Jagaraj, A. M. G. Ragagnin, J. D. Atkin

Research output: Contribution to journalReview articleResearchpeer-review

Abstract

Rab GTPases are becoming increasingly implicated in neurodegenerative disorders, although their role in amyotrophic lateral sclerosis (ALS) has been somewhat overlooked. However, dysfunction of intracellular transport is gaining increasing attention as a pathogenic mechanism in ALS. Many previous studies have focused axonal trafficking, and the extreme length of axons in motor neurons may contribute to their unique susceptibility in this disorder. In contrast, the role of transport defects within the cell body has been relatively neglected. Similarly, whilst Rab GTPases control all intracellular membrane trafficking events, their role in ALS is poorly understood. Emerging evidence now highlights this family of proteins in ALS, particularly the discovery that C9orf72 functions in intra transport in conjunction with several Rab GTPases. Here, we summarize recent updates on cellular transport defects in ALS, with a focus on Rab GTPases and how their dysfunction may specifically target neurons and contribute to pathophysiology. We discuss the molecular mechanisms associated with dysfunction of Rab proteins in ALS. Finally, we also discuss dysfunction in other modes of transport recently implicated in ALS, including nucleocytoplasmic transport and the ER-mitochondrial contact regions (MAM compartment), and speculate whether these may also involve Rab GTPases.

LanguageEnglish
Pages623-651
Number of pages29
JournalCritical Reviews in Biochemistry and Molecular Biology
Volume53
Issue number6
DOIs
Publication statusPublished - 2 Nov 2018

Fingerprint

rab GTP-Binding Proteins
Amyotrophic Lateral Sclerosis
Neurons
Defects
Intracellular Membranes
Cell Nucleus Active Transport
Proteins
Motor Neurons
Cells
Neurodegenerative Diseases
Membranes
Axons

Keywords

  • Amyotrophic lateral sclerosis
  • cellular trafficking
  • motor neuron disease
  • neurodegeneration
  • Rab GTPases

Cite this

Parakh, S. ; Perri, E. R. ; Jagaraj, C. J. ; Ragagnin, A. M. G. ; Atkin, J. D. / Rab-dependent cellular trafficking and amyotrophic lateral sclerosis. In: Critical Reviews in Biochemistry and Molecular Biology. 2018 ; Vol. 53, No. 6. pp. 623-651.
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Rab-dependent cellular trafficking and amyotrophic lateral sclerosis. / Parakh, S.; Perri, E. R.; Jagaraj, C. J.; Ragagnin, A. M. G.; Atkin, J. D.

In: Critical Reviews in Biochemistry and Molecular Biology, Vol. 53, No. 6, 02.11.2018, p. 623-651.

Research output: Contribution to journalReview articleResearchpeer-review

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