Hunter S Richardson's research while affiliated with National Institutes of Health and other places

Oligodendrocytes have elaborate arbors of microtubules that extend toward axons and spiral around myelin sheaths. Oligodendrocytes rely on satellite organelles called Golgi outposts to nucleate new microtubules at sites far from the cell body. We now show that the Golgi outpost marker TPPP (tubulin polymerization promoting protein) forms liquid condensates that co-partition with tubulin in order to nucleate microtubules. In oligodendrocytes, TPPP forms either dynamic puncta or aberrant microtubule-associated aggregates. In Multiple System Atrophy (MSA), a sequela of histological events initiates with TPPP aggregation in myelin sheaths and terminates in perinuclear TPPP co-aggregation with alpha-synuclein (aSyn). Finally, recombinant TPPP aggregates are toxic to primary oligodendrocytes. Thus, while the liquid condensate property of TPPP facilitates microtubule nucleation, it also predisposes TPPP to aggregate in disease.

Both neurons and glia in mammalian brains are highly rami-fied. Neurons form complex neural networks using axons and dendrites. Axons are long with few branches and form pre-synaptic boutons that connect to target neurons and effector tissues. Dendrites are shorter, highly branched, and form post-synaptic boutons. Astrocyte processes contact synapses and blood vessels in order to regulate neuronal activity and blood flow, respectively. Oligodendrocyte processes extend toward axons to make myelin sheaths. Microglia processes dynamically survey their environments. Here, we describe the local secretory system (ER and Golgi) in neuronal and glial processes. We focus on Golgi outpost functions in acentrosomal microtubule nucleation, cargo trafficking, and protein glyco-sylation. Thus, satellite ER and Golgi are critical for local structure and function in neurons and glia.