LRRk2 expression and localization

LRRK2 mRNA displays near ubiquitous localization throughout the mouse and human brain, with particular concentration within neurons of the cortex, striatum, and
hippocampus. Protein distributes in a likewise manner, detectable in the vulnerable neurons of the substantia nigra pars compacta. LRRK2 displays particularly high expression in the kidney and appears to increase in expression on organogenesis and cell maturation. LRRK2 adopts a punctate intracellular cytosolic localization
that associates with various membranous structures including vesicles, mitochondria, Golgi, and the ER. Biochemical fractionation suggests that LRRK2 resides on the
cytoplasmic side of membrane-containing organelles without evidence of nuclear or mitochondrial internalization. Similar to a-syn, clear orthologues to LRRK2 have been
identified in all described mammalian genomes, but in invertebrates, orthologous genes may show closer homology to mammalian LRRK1 than to the LRRK2 gene. Close sequence homology and overlapping expression profiles between the LRRK1 and LRRK2 genes suggests redundancy in function. LRRK2-deficient mice are viable with no dramatic abnormalities, although detailed reports have not been published. Loss of the LRRK orthologues in Drosophila seems to produce a strain-dependent phenotype, and additional studies will help resolve the controversy. Loss of
LRRK orthologues in nematodes produces defects in vesicle sorting, whereas loss in slime mold produces defects in chemotaxis.