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. 2020 Jul 28;14:158. doi: 10.3389/fncel.2020.00158

Figure 1.

Figure 1

Striatal synaptic effects of leucine-rich repeatkinase 2 (LRRK2). LRRK2 is thought to influence striatal synaptogenesis interacting with cytoskeleton and microtubules ①. The modulation of presynaptic voltage-gated Ca2+ channels (CaV2.1; ②), as well as the regulation of synaptic vesicle exocytosis, endocytosis, and recycling ③, could influence the release of glutamate (Glu) from the corticostriatal excitatory terminal ④. Moreover, the postsynaptic expression of glutamatergic AMPAR could be influenced by LRRK2 activity ⑤. LRRK2 could alter striatal DAergic transmission ⑥ inducing midbrain neuronal loss or DAergic terminals abnormalities, including abnormal DAT activity ⑦ and pathological α-synuclein aggregation ⑧. The postsynaptic expression and function of DA receptors can be influenced by mutant LRRK2, including altered D2R-dependent postsynaptic synthesis of endocannabinoids (eCBs; ⑨) and D1R expression/internalization ⑩. Finally, the dysfunction of PKA and DARPP32 pathways ⑪ and the impairment of intracellular AMPAR exocytosis ⑫ may result in altered synaptic long-term changes. AC, adenylate cyclase; CaMKII, Ca2+-calmodulin dependent protein kinase II; cAMP, 3′,5′-cyclic adenosine monophosphate; CB1R, cannabinoid receptor type 1; ER, endoplasmic reticulum; IP3, inositol trisphosphate; PLC, phospholipase C.