Northern blot analysis detected a 9-kb m RNA transcript in all tissues tested, including brain.
Highest transcript levels were obtained in the putamen, substantia nigra, and lung.
Coexpression of DVL1 increased LRRK2 steady-state protein levels, an effect that was dependent on the DEP domain.
LRRK2-DVL1-3 interactions were disrupted by the LRRK2 Y1699C mutation (609007.0002), whereas pathogenic mutations at residues arg1441 (see, e.g., 609007.0001) and arg1728 strengthened LRRK2-DVL1 interactions.
No differences were observed between normal brains and those from individuals with Parkinson disease.
Similar studies on rodent brain showed Lrrk2 expression in the striatum and absence of Lrrk2 expression in the midbrain.
Coexpression of DVL1 with LRRK2 in mammalian cells resulted in the redistribution of LRRK2 to typical cytoplasmic DVL1 aggregates in HEK293 and SH-SY5Y cells and colocalization in neurites and growth cones of differentiated dopaminergic SH-SY5Y cells.
Since the DVL1 DEP domain is known to be involved in the regulation of small GTPases, 19625296, images] [Full Text]" pmid="19625296"Gehrke et al.
LRRK2 interacted preferentially with the C-terminal R2 RING finger domain of parkin, and parkin interacted with the COR domain of LRRK2.
Coexpression of LRRK2 and parkin increased cytoplasmic protein aggregates that contained LRRK2 and enhanced the ubiquitination of these aggregates.
The interaction was guanine-nucleotide independent. Endogenous LRRK2 protein was found to colocalize with alpha/beta-tubulin in the cell body and neuronal processes of rat primary hippocampal neurons.
These findings linked LRRK2 with microtubules, a structural component of the cell critically involved in the pathogenesis of several neurodegenerative diseases, including Parkinson disease.
(2004) identified a putative disease-causing transcript (DKFZp434H2111) within a 2.6-Mb region encompassing a locus for Parkinson disease-8 (PARK8; 607060).