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PubMed:21454543 JSONTXT 32 Projects

Annnotations TAB TSV DIC JSON TextAE Lectin_function

Id Subject Object Predicate Lexical cue
T1 0-94 Sentence denotes Rac1 protein rescues neurite retraction caused by G2019S leucine-rich repeat kinase 2 (LRRK2).
T2 95-293 Sentence denotes Mutations in leucine-rich repeat kinase 2 (LRRK2) are currently the most common genetic cause of familial late-onset Parkinson disease, which is clinically indistinguishable from idiopathic disease.
T3 294-393 Sentence denotes The most common pathological mutation in LRRK2, G2019S LRRK2, is known to cause neurite retraction.
T4 394-485 Sentence denotes However, molecular mechanisms underlying regulation of neurite length by LRRK2 are unknown.
T5 486-680 Sentence denotes Here, we demonstrate a novel interaction between LRRK2 and the Rho GTPase, Rac1, which plays a critical role in actin cytoskeleton remodeling necessary for the maintenance of neurite morphology.
T6 681-794 Sentence denotes LRRK2 binds strongly to endogenous or expressed Rac1, while showing weak binding to Cdc42 and no binding to RhoA.
T7 795-948 Sentence denotes Co-expression with LRRK2 increases Rac1 activity, as shown by increased binding to the p21-activated kinase, which modulates actin cytoskeletal dynamics.
T8 949-1054 Sentence denotes LRRK2 constructs carrying mutations that inactivate the kinase or GTPase activities do not activate Rac1.
T9 1055-1292 Sentence denotes Interestingly, LRRK2 does not increase levels of membrane-bound Rac1 but dramatically changes the cellular localization of Rac1, causing polarization, which is augmented further when LRRK2 is co-expressed with constitutively active Rac1.
T10 1293-1497 Sentence denotes Four different disease-related mutations in LRRK2 altered binding to Rac1, with the G2019S and R1441C LRRK2 mutations attenuating Rac1 binding and the Y1699C and I2020T LRRK2 mutations increasing binding.
T11 1498-1592 Sentence denotes Co-expressing Rac1 in SH-SY5Y cells rescues the G2019S mutant phenotype of neurite retraction.
T12 1593-1746 Sentence denotes We hypothesize that pathological mutations in LRRK2 attenuates activation of Rac1, causing disassembly of actin filaments, leading to neurite retraction.
T13 1747-1930 Sentence denotes The interactions between LRRK2 and Rho GTPases provide a novel pathway through which LRRK2 might modulate cellular dynamics and contribute to the pathophysiology of Parkinson disease.