Dictyostelium discoideum as a model host for meningococcal pathogenesis.

Background: The aim of the present study was to evaluate the possibility of studying meningococcal virulence in a new model organism, Dictyostelium discoideum, a haploid social soil amoeba that is an established host model for several human pathogens, leading to the discovery of novel virulence mechanisms.

Material/methods: A number of virulent and hyper-virulent N. meningitidis strains, including isogenic encapsulated, unencapsulated, and lipooligosaccharide (LOS) outer core-defective derivatives, were used to test the ability of D.

Functional characterization of Rab7 mutant proteins associated with Charcot-Marie-Tooth type 2B disease.

Charcot-Marie-Tooth (CMT) type 2 neuropathies are a group of autosomal-dominant axonal disorders genetically and clinically heterogeneous. In particular, CMT type 2B (CMT2B) neuropathies are characterized by severe sensory loss, often complicated by infections, arthropathy, and amputations. Recently, four missense mutations in the small GTPase Rab7 associated with the Charcot-Marie Tooth type 2B phenotype have been identified.

Expression, assay, and functional properties of RILP.

Rab proteins are master regulators of vesicular membrane traffic of endocytic and exocytic pathways. They basically serve to recruit proteins and lipids required for vesicle formation, docking, and fusion. Each Rab protein is able to recruit one or more effectors, and, through the action of effectors, it drives its specific downstream functions.

The Rab-interacting lysosomal protein, a Rab7 and Rab34 effector, is capable of self-interaction.

Rab-interacting lysosomal protein (RILP) has been identified as an interacting partner of the small GTPases Rab7 and Rab34. Active Rab7 recruits RILP on the late endosomal/lysosomal membrane and RILP then functions as a Rab7 effector controlling transport to degradative compartments. Indeed, RILP induces recruitment of dynein-dynactin motor complexes to Rab7-containing late endosomes and lysosomes.