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Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag
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Cellular effects mediated by pathogenic LRRK2: homing in on Rab-mediated processes

Jesús Madero-Pérez1, Elena Fdez1, Belén Fernández1

  • 1Institute of Parasitology and Biomedicine 'López-Neyra', Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, Granada 18016, Spain.

Biochemical Society Transactions
|February 17, 2017
PubMed

Insights

Leucine-rich repeat kinase 2 (LRRK2) is implicated in Parkinson's disease pathogenesis. This review links LRRK2's role in cellular trafficking deficits to its newly identified kinase substrates.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Leucine-rich repeat kinase 2 (LRRK2) is a key factor in Parkinson's disease (PD) development.
  • LRRK2 mutations increase its kinase activity, leading to cytotoxicity, suggesting kinase inhibitors as potential therapeutics.
  • Understanding cellular deficits caused by pathogenic LRRK2 and its substrates is crucial for developing effective treatments.

Purpose of the Study:

  • To review the connection between intracellular trafficking defects and LRRK2-mediated phosphorylation.
  • To highlight newly identified LRRK2 kinase substrates involved in cellular processes.

Main Methods:

  • Literature review of studies on LRRK2, Parkinson's disease, and intracellular trafficking.
  • Analysis of recent findings on LRRK2 phosphorylation targets.
  • Synthesis of information linking LRRK2 activity to cellular dysfunction.

Main Results:

  • LRRK2 is consistently shown to impair intracellular vesicular trafficking.
  • A subset of proteins critical for trafficking are phosphorylated by LRRK2.
  • These substrates are intricately involved in the cellular deficits observed in PD.

Conclusions:

  • Pathogenic LRRK2 disrupts cellular functions through the phosphorylation of specific trafficking-related substrates.
  • Targeting LRRK2 kinase activity or its substrates may offer disease-modifying strategies for Parkinson's disease.
  • Further research into LRRK2 substrates is essential for understanding PD pathogenesis and developing novel therapies.
Keywords:
GDIGEFREPRab proteinleucine-rich repeat kinasevesicular trafficking

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