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. 2021 Jul 26;11(8):1101. doi: 10.3390/biom11081101

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Current (simplified) model of the LRRK2 cycle. LRRK2 exists as monomers in the cytosol, where it is stabilized by 14-3-3 proteins. Upon binding to Rab proteins, LRRK2 is recruited to biological membranes, where the kinase domain of LRRK2 gets activated, the GTP hydrolyzes, and the protein dimerizes. The exact order in which these processes happen is unknown, but it is possible that they occur simultaneously. After the signaling output is achieved, GDP is exchanged to GTP, and the protein monomerizes and gets translocated to the cytosol. The figure is based on reference [52]. Association to microtubules was left out on purpose, as it remains to be experimentally proven to be true for endogenous LRRK2; figure created with BioRender.com (access date 2 April 2021).