Mitf is a Schwann cell sensor of axonal integrity that drives nerve repair.

Schwann cells respond to acute axon damage by transiently transdifferentiating into specialized repair cells that restore sensorimotor function. However, the molecular systems controlling repair cell formation and function are not well defined, and consequently, it is unclear whether this form of cellular plasticity has a role in peripheral neuropathies. Here, we identify Mitf as a transcriptional sensor of axon damage under the control of Nrg-ErbB-PI3K-PI5K-mTorc2 signaling.

Live Cell Imaging of Yeast Golgi Dynamics.

Fluorescence imaging of live cells allows for the observation of dynamic processes inside cells in real time. Here we describe a strategy to image clathrin-coated vesicle dynamics in a single focal plane at the trans-Golgi network of the yeast Saccharomyces cerevisiae. This method can be readily adapted for live cell imaging of a diverse set of dynamic processes within cells.

A hidden threshold in motor neuron gene networks revealed by modulation of miR-218 dose.

Disruption of homeostatic microRNA (miRNA) expression levels is known to cause human neuropathology. However, the gene regulatory and phenotypic effects of altering a miRNA's in vivo abundance (rather than its binary gain or loss) are not well understood. By genetic combination, we generated an allelic series of mice expressing varying levels of miR-218, a motor neuron-selective gene regulator associated with motor neuron disease.

Human genetics and neuropathology suggest a link between miR-218 and amyotrophic lateral sclerosis pathophysiology.

Motor neuron-specific microRNA-218 (miR-218) has recently received attention because of its roles in mouse development. However, miR-218 relevance to human motor neuron disease was not yet explored. Here, we demonstrate by neuropathology that miR-218 is abundant in healthy human motor neurons.

Clathrin Adaptor Complex-interacting Protein Irc6 Functions through the Conserved C-Terminal Domain.

Clathrin coats drive transport vesicle formation from the plasma membrane and in pathways between the trans-Golgi network (TGN) and endosomes. Clathrin adaptors play central roles orchestrating assembly of clathrin coats. The yeast clathrin adaptor-interacting protein Irc6 is an orthologue of human p34, which is mutated in the inherited skin disorder punctate palmoplantar keratoderma type I.

Conserved role for Gga proteins in phosphatidylinositol 4-kinase localization to the -Golgi network.

Phosphoinositides serve as key membrane determinants for assembly of clathrin coat proteins that drive formation of clathrin-coated vesicles. At the -Golgi network (TGN), phosphatidylinositol 4-phosphate (PtdIns4P) plays important roles in recruitment of two major clathrin adaptors, Gga (Golgi-localized, gamma-adaptin ear homology, Arf-binding) proteins and the AP-1 (assembly protein-1) complex. The molecular mechanisms that mediate localization of phosphatidylinositol kinases responsible for synthesis of PtdIns4P at the TGN are not well characterized.

Yeast Irc6p is a novel type of conserved clathrin coat accessory factor related to small G proteins.

Clathrin coat accessory proteins play key roles in transport mediated by clathrin-coated vesicles. Yeast Irc6p and the related mammalian p34 are putative clathrin accessory proteins that interact with clathrin adaptor complexes. We present evidence that Irc6p functions in clathrin-mediated traffic between the trans-Golgi network and endosomes, linking clathrin adaptor complex AP-1 and the Rab GTPase Ypt31p.

Phosphoinositide-mediated clathrin adaptor progression at the trans-Golgi network.

Clathrin-coated vesicles mediate endocytosis and transport between the trans-Golgi network (TGN) and endosomes in eukaryotic cells. Clathrin adaptors play central roles in coat assembly, interacting with clathrin, cargo and membranes. Two main types of clathrin adaptor act in TGN-endosome traffic: GGA proteins and the AP-1 complex.

Distinct roles for TGN/endosome epsin-like adaptors Ent3p and Ent5p.

Clathrin adaptors are key factors in clathrin-coated vesicle formation, coupling clathrin to cargo and/or the lipid bilayer. A physically interacting network of three classes of adaptors participate in clathrin-mediated traffic between the trans-Golgi network (TGN) and endosomes: AP-1, Gga proteins, and epsin-like proteins. Here we investigate functional relationships within this network through transport assays and protein localization analysis in living yeast cells.

Yeast epsin-related proteins required for Golgi-endosome traffic define a gamma-adaptin ear-binding motif.

Clathrin-coated vesicles (CCVs) are a central component of endocytosis and traffic between the trans-Golgi network (TGN) and endosomes. Although endocytic CCV formation is well characterized, much less is known about CCV formation at internal membranes. Here we describe two epsin amino-terminal homology (ENTH) domain-containing proteins, Ent3p and Ent5p, that are intimately involved in clathrin function at the Golgi.