LRRK2 Affects Vesicle Trafficking, Neurotransmitter Extracellular Level and Membrane Receptor Localization

Rossana Migheli, Maria Grazia Del Giudice, Ylenia Spissu, Giovanna Sanna, Yulan Xiong, Ted M. Dawson, Valina L. Dawson, Manuela Galioto, Gaia Rocchitta, Alice Biosa, Pier Andrea Serra, Maria Teresa Carri, Claudia Crosio, Ciro Iaccarino

Research output: Contribution to journalArticle

Abstract

The leucine-rich repeat kinase 2 (LRRK2) gene was found to play a role in the pathogenesis of both familial and sporadic Parkinson's disease (PD). LRRK2 encodes a large multi-domain protein that is expressed in different tissues. To date, the physiological and pathological functions of LRRK2 are not clearly defined. In this study we have explored the role of LRRK2 in controlling vesicle trafficking in different cellular or animal models and using various readouts. In neuronal cells, the presence of LRRK2G2019S pathological mutant determines increased extracellular dopamine levels either under basal conditions or upon nicotine stimulation. Moreover, mutant LRRK2 affects the levels of dopamine receptor D1 on the membrane surface in neuronal cells or animal models. Ultrastructural analysis of PC12-derived cells expressing mutant LRRK2G2019S shows an altered intracellular vesicle distribution. Taken together, our results point to the key role of LRRK2 to control vesicle trafficking in neuronal cells.

Original languageEnglish
Article numbere77198
JournalPLoS One
Volume8
Issue number10
DOIs
Publication statusPublished - Oct 22 2013

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Migheli, R., Del Giudice, M. G., Spissu, Y., Sanna, G., Xiong, Y., Dawson, T. M., Dawson, V. L., Galioto, M., Rocchitta, G., Biosa, A., Serra, P. A., Carri, M. T., Crosio, C., & Iaccarino, C. (2013). LRRK2 Affects Vesicle Trafficking, Neurotransmitter Extracellular Level and Membrane Receptor Localization. PLoS One, 8(10), [e77198]. https://doi.org/10.1371/journal.pone.0077198