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Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells
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The ALS8 protein VAPB interacts with the ER-Golgi recycling protein YIF1A and regulates membrane delivery into

Marijn Kuijpers1, Ka Lou Yu, Eva Teuling

  • 1Division of Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.

The EMBO Journal
|June 6, 2013
PubMed

Insights

Vesicle-associated membrane protein B (VAPB) and Yip1-interacting factor homologue A (YIF1A) are crucial for neuronal transport. Mutant VAPB disrupts YIF1A localization, potentially causing motor neuron disease.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Vesicle-associated membrane protein B (VAPB) is an ER-localized protein implicated in amyotrophic lateral sclerosis type 8 (ALS8).
  • The function of wild-type and mutant VAPB in neuronal pathways remains largely unclear.
  • Understanding VAPB's interactions is key to elucidating its role in neurodegeneration.

Purpose of the Study:

  • To identify novel VAPB binding partners.
  • To investigate the role of VAPB and its interaction with YIF1A in neuronal intracellular transport.
  • To explore the impact of VAPB mutations on YIF1A localization and function.

Main Methods:

  • Co-immunoprecipitation to identify VAPB binding partners.
  • Confocal microscopy to analyze protein localization in rat hippocampal neurons.
  • Analysis of dendritic morphology and intracellular trafficking.

Main Results:

  • Yip1-interacting factor homologue A (YIF1A) was identified as a novel VAPB binding partner involved in the early secretory pathway.
  • VAPB regulates YIF1A localization, recycling between the ER and Golgi, primarily in ER-Golgi intermediate compartments (ERGICs).
  • The ALS8-associated VAPB-P56S mutation causes YIF1A mislocalization to VAPB clusters, disrupting ERGIC localization and affecting dendritic morphology.

Conclusions:

  • Both VAPB and YIF1A are essential for ER-to-Golgi transport and neuronal structure.
  • The mislocalization of YIF1A due to VAPB mutations may contribute to the pathogenesis of VAPB-associated motor neuron diseases.
  • This study reveals a new mechanism involving VAPB and YIF1A in maintaining neuronal health and transport.

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