Mutations in LRRK2 cause autosomal dominant Parkinson's disease (PD). LRRK2 
encodes a multi-domain protein containing GTPase and kinase domains, and 
putative protein-protein interaction domains. Familial PD mutations alter the 
GTPase and kinase activity of LRRK2 in vitro. LRRK2 is suggested to regulate a 
number of cellular pathways although the underlying mechanisms are poorly 
understood. To explore such mechanisms, it has proved informative to identify 
LRRK2-interacting proteins, some of which serve as LRRK2 kinase substrates. 
Here, we identify common interactions of LRRK2 with members of the dynamin 
GTPase superfamily. LRRK2 interacts with dynamin 1-3 that mediate membrane 
scission in clathrin-mediated endocytosis and with dynamin-related proteins that 
mediate mitochondrial fission (Drp1) and fusion (mitofusins and OPA1). LRRK2 
partially co-localizes with endosomal dynamin-1 or with mitofusins and OPA1 at 
mitochondrial membranes. The subcellular distribution and oligomeric complexes 
of dynamin GTPases are not altered by modulating LRRK2 in mouse brain, whereas 
mature OPA1 levels are reduced in G2019S PD brains. LRRK2 enhances mitofusin-1 
GTP binding, whereas dynamin-1 and OPA1 serve as modest substrates of 
LRRK2-mediated phosphorylation in vitro. While dynamin GTPase orthologs are not 
required for LRRK2-induced toxicity in yeast, LRRK2 functionally interacts with 
dynamin-1 and mitofusin-1 in cultured neurons. LRRK2 attenuates neurite 
shortening induced by dynamin-1 by reducing its levels, whereas LRRK2 rescues 
impaired neurite outgrowth induced by mitofusin-1 potentially by reversing 
excessive mitochondrial fusion. Our study elucidates novel functional 
interactions of LRRK2 with dynamin-superfamily GTPases that implicate LRRK2 in 
the regulation of membrane dynamics important for endocytosis and mitochondrial 
morphology.