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Tied up: Does altering phosphoinositide-mediated membrane trafficking influence neurodegenerative disease phenotypes?

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Abstract

Phosphoinositides are a class of membrane lipids that are found on several intracellular compartments and play diverse roles inside cells, such as vesicle formation, protein trafficking, endocytosis etc. Intracellular distribution and levels of phosphoinositides are regulated by enzymes that generate and breakdown these lipids as well as other proteins that associate with phosphoinositides. These events lead to differing levels of specific phosphoinositides on different intracellular compartments. At these intracellular locations, phosphoinositides and their associated proteins, such as Rab GTPases, dynamin and BAR domain-containing proteins, regulate a variety of membrane trafficking pathways. Neurodegenerative phenotypes in disorders such as Parkinson’s disease (PD) can arise as a consequence of altered or hampered intracellular trafficking. Altered trafficking can cause proteins such as \(\upalpha \)-synuclein to aggregate intracellularly. Several trafficking pathways are regulated by master regulators such as LRRK2, which is known to regulate the activity of phosphoinositide effector proteins. Perturbing either the levels of phosphoinositides or their interactions with different proteins disrupts intracellular trafficking pathways, contributing to phenotypes often observed in disorders such as Alzheimer’s or PDs. Thus, studying phosphoinositide regulation and its role in trafficking can give us a deeper understanding of the contribution of disrupted trafficking to neurodegenerative phenotypes.

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Acknowledgements

We thank Amruta Vasudevan for comments on the manuscript. Research in the SPK lab is supported by HHMI-IECS to SPK and by TIFR.

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  1. Sravanthi S. P. Nadiminti and Madhushree Kamak contributed equally to this work.

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  1. Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, 400 005, India

    Sravanthi S. P. Nadiminti, Madhushree Kamak & Sandhya P. Koushika

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  1. Sravanthi S. P. Nadiminti
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  2. Madhushree Kamak
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Correspondence to Sandhya P. Koushika.

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Nadiminti, S.S.P., Kamak, M. & Koushika, S.P. Tied up: Does altering phosphoinositide-mediated membrane trafficking influence neurodegenerative disease phenotypes?. J Genet 97, 753–771 (2018). https://doi.org/10.1007/s12041-018-0961-5

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  • DOI: https://doi.org/10.1007/s12041-018-0961-5

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