Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity.

ABSTRACT: Most monogenic cases of obesity in humans have been linked to mutations in genes encoding members of the leptin-melanocortin pathway. Specifically, mutations in MC4R, the melanocortin-4 receptor gene, account for 3-5% of all severe obesity cases in humans^1-3. Recently, ADCY3 (adenylyl cyclase 3) gene mutations have been implicated in obesity^4,5. ADCY3 localizes to the primary cilia of neurons ⁶ , organelles that function as hubs for select signaling pathways. Mutations that disrupt the functions of primary cilia cause ciliopathies, rare recessive pleiotropic diseases in which obesity is a cardinal manifestation ⁷ . We demonstrate that MC4R colocalizes with ADCY3 at the primary cilia of a subset of hypothalamic neurons, that obesity-associated MC4

SUBMITTER: Siljee JE 

PROVIDER: S-EPMC5805646 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature