title: Golgi trafficking defects in postnatal microcephaly: The evidence for "Golgipathies".
abstract: The Golgi apparatus plays a central role in cell homeostasis, not only in processing and maturing newly synthesized proteins and lipids but also in orchestrating their sorting, packing, routing and recycling on the way to their final destination. These multiple secretory pathways require a complex ballet of vesicular and tubular carriers that continuously bud off from donor membranes and fuse to acceptor membranes. Membrane trafficking is particularly prominent in axons, where cargo molecules have a long way to travel before they reach the synapse, and in oligodendrocytes, which require an immense increase in membrane surface in order to sheathe axons in myelin. Interestingly, in recent years, genes encoding Golgi-associated proteins with a role in membrane trafficking have been found to be defective in an increasing number of inherited disorders whose clinical manifestations include postnatal-onset microcephaly (POM), white matter defects and intellectual disability. Several of these genes encode RAB GTPases, RAB-effectors or RAB-regulating proteins, linking POM and intellectual disability to RAB-dependent Golgi trafficking pathways and suggesting that their regulation is critical to postnatal brain maturation and function. Here, we review the key roles of the Golgi apparatus in post-mitotic neurons and the oligodendrocytes that myelinate them, and provide an overview of these Golgi-associated POM-causing genes, their function in Golgi organization and trafficking and the likely mechanisms that may link dysfunctions in RAB-dependent regulatory pathways with POM.
authors.affiliation: PROTECT, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France; AP HP, Hôpital Robert Debré, Service de Génétique Clinique, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Passemard
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR144, Paris, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Perez
authors.affiliation: PROTECT, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Institut Curie, PSL Research University, CNRS, UMR144, Paris, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Colin-Lemesre
authors.affiliation: PROTECT, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Sowmyalakshmi
authors.initials: S
authors.lastname: Rasika
authors.affiliation: PROTECT, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, United Kingdom.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gressens
authors.affiliation: PROTECT, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France. Electronic address: vincent.elghouzzi@inserm.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: El Ghouzzi
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D002462:Cell Membrane / Q000378:metabolism; D019317:Evidence-Based Medicine; D006056:Golgi Apparatus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008831:Microcephaly / Q000473:pathology* / Q000503:physiopathology*; D008959:Models, Neurological; D021381:Protein Transport; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D020691:rab GTP-Binding Proteins
keywords: Golgi apparatus; Golgipathies; Intellectual disability; Neuronal trafficking; Postnatal microcephaly; RAB GTPase