LRRK2 regulates synaptogenesis and dopamine receptor activation through modulation of PKA activity

The authors show that leucine-rich repeat kinase 2 (Lrrk2) binds protein kinase A (PKA) regulatory subunit IIβ to decrease PKA activity in striatal projection neurons (SPNs). Lrrk2 regulation of PKA prevents its synaptic translocation, altering synaptogenesis and transmission in developing SPNs. A Parkinson's disease–associated mutant of Lrrk2 prevented its interaction with PKARIIβ.