Fear Deficits in Hypomyelinated Tppp Knockout Mice.
Oligodendrocytes in the central nervous system (CNS) produce myelin sheaths that insulate axons to facilitate efficient electrical conduction. These myelin sheaths contain lamellar microtubules that enable vesicular transport into the inner sheath. Mechanistically, oligodendrocytes rely on Golgi outpost organelles and the associated protein tubulin polymerization promoting protein (TPPP) to nucleate or form new microtubules outside of the cell body. Consequently, elongation of lamellar microtubules is defective in Tppp knockout (KO) mice, which have thinner and shorter myelin sheaths. We now explore the behavioral phenotypes of Tppp KO mice using a number of different assays. In open-field assays, Tppp KO mice display similar activity levels and movement patterns as wildtype mice, indicating that they do not display anxiety behavior. However, Tppp KO mice lack fear responses by two types of assays, traditional fear-conditioning assays and looming fear assays, which test for innate fear responses. Deficits in fear-conditioning, which is a memory dependent task, as well as in spatial memory tests support possible short-term memory defects in Tppp KO mice. Together, our experiments indicate a connection between CNS myelination and behavioral deficits.SIGNIFICANCE STATEMENT Oligodendrocytes are cells in the brain that make myelin sheaths, which wrap concentrically around axons to provide insulation that facilitates electrical conduction. Fear responses have historically been attributed to neuronal activity. However, emerging literature indicates that mouse models with defective myelination display long-term fear deficits. Here, we look at a specific mouse model that lacks an oligodendrocyte-specific protein that is important for building the cellular structure of microtubules, which allow for transport to and along the myelin sheath. These mice display deficits in both memory-dependent fear as well as innate fear responses. Thus, our work indicates that myelin structure is important for fear response.
View details for DOI 10.1523/ENEURO.0170-20.2020
View details for PubMedID 32878961
Golgi Outposts Nucleate Microtubules in Cells with Specialized Shapes.
Trends in cell biology
Classically, animal cells nucleate or form new microtubules off the perinuclear centrosome. In recent years, the Golgi outpost has emerged as a satellite organelle that can function as an acentrosomal microtubule-organizing center (MTOC), nucleating new microtubules at distances far from the nucleus or cell body. Golgi outposts can nucleate new microtubules in specialized cells with unique cytoarchitectures, including Drosophila neurons, mouse muscle cells, and rodent oligodendrocytes. This review compares and contrasts topics of functional relevance, including Golgi outpost heterogeneity, formation and transport, as well as regulation of microtubule polarity and branching. Golgi outposts have also been implicated in the pathology of diseases including muscular dystrophy, and neurodegenerative diseases, such as Parkinson's disease (PD). Since Golgi outposts are relatively understudied, many outstanding questions regarding their function and roles in disease remain.
View details for DOI 10.1016/j.tcb.2020.07.004
View details for PubMedID 32863092