Schizophrenia: the "BLOC" may be in the endosomes.

Full Abstract

Genome-wide association studies have identified multiple genetic polymorphisms associated with schizophrenia. These polymorphisms conform to a polygenic disease model in which multiple alleles cumulatively increase the risk of developing disease. Two genes linked to schizophrenia, DTNBP1 and MUTED, encode proteins that belong to the endosome-localized Biogenesis of Lysosome-related Organelles Complex-1 (BLOC-1). BLOC-1 plays a key role in endosomal trafficking and as such has been found to regulate cell-surface abundance of the D2 dopamine receptor, the biogenesis and fusion of synaptic vesicles, and neurite outgrowth. These functions are pertinent to both neurodevelopment and synaptic transmission, processes tightly regulated by selective cell-surface delivery of membrane proteins to and from endosomes. We propose that cellular processes, such as endosomal trafficking, act as convergence points in which multiple small effects from polygenic genetic polymorphisms accumulate to promote the development of schizophrenia.

Author information

Author/s: Ryder, Pearl V (PV); Faundez, Victor (V);

Affiliation: Graduate Program in Biochemistry, Cell, and Developmental Biology, Emory University, Atlanta, GA 30322, USA.

Journal and publication information

Publication Type: Journal Article

Journal: Science signaling (Sci Signal), published in United States. (Language: eng)

Reference: 2009-; vol 2 (issue 93) : pp pe66

Dates: Created 2009/10/21; Completed 2009/11/04;

PMID: 19843956, status: MEDLINE (last retrieval date: 11/4/2009, IMS Date: )

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