Defects in the COG complex and COG-related trafficking regulators affect neuronal Golgi function

Abstract

The Conserved Oligomeric Golgi (COG) complex is an evolutionarily conserved hetero-octameric protein complex that has been proposed to organize vesicle tethering at the Golgi apparatus. Defects in seven of the eight COG subunits are linked to Congenital Disorders of Glycosylation (CDG)-type II, a family of rare diseases involving misregulation of protein glycosylation, alterations in Golgi structure, variations in retrograde trafficking through the Golgi and system-wide clinical pathologies. A troublesome aspect of these diseases are the neurological pathologies such as low IQ, microcephaly, and cerebellar atrophy. The essential function of the COG complex is dependent upon interactions with other components of trafficking machinery, such as Rab-GTPases and SNAREs. COG-interacting Rabs and SNAREs have been implicated in neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. Defects in Golgi maintenance disrupts trafficking and processing of essential proteins, frequently associated with and contributing to compromised neuron function and human disease. Despite the recent advances in molecular neuroscience, the subcellular bases for most neurodegenerative diseases are poorly understood. This article gives an overview of the potential contributions of the COG complex and its Rab and SNARE partners in the pathogenesis of different neurodegenerative disorders.

Keywords: COG; Rab; SNARE; congenital disorders of glycosylation; conserved oligomeric Golgi complex; glycosylation; neurodegeneration; vesicular trafficking.

Figure 1

Model of COG trafficking within neurons. A cartoon depicting the proposed roles for the COG complex (depicted as red shapes for lobe A and green shapes for lobe B subcomplexes) and its interacting protein partners in Golgi trafficking: Rabs (yellow circles), and SNAREs (purple lines). Right panel: Immunofluorescence images of COG complex subunit COG3 (top-red) and Golgi SNARE GS15 (middle-green) in rat dorsal root ganglion. Perinuclear (DAPI) co-localization is indicated by yellow in the merged image (bottom). Scale Bar = 10 μm.