The large GTPase dynamin 2 is a key player in membrane and cytoskeletal dynamics 
mutated in centronuclear myopathy (CNM) and Charcot-Marie Tooth (CMT) 
neuropathy, two discrete dominant neuromuscular disorders affecting skeletal 
muscle and peripheral nerves respectively. The molecular basis for the 
tissue-specific phenotypes observed and the physiopathological mechanisms linked 
to dynamin 2 mutations are not well established. In this study, we have analyzed 
the impact of CNM and CMT implicated dynamin 2 mutants using ectopic expression 
of four CNM and two CMT mutations, and patient fibroblasts harboring two dynamin 
2 CNM mutations in established cellular processes of dynamin 2 action. Wild type 
and CMT mutants were seen in association with microtubules whereas CNM mutants 
lacked microtubules association and did not disrupt interphase microtubules 
dynamics. Most dynamin 2 mutants partially decreased clathrin-mediated 
endocytosis when ectopically expressed in cultured cells; however, experiments 
in patient fibroblasts suggested that endocytosis is overall not defective. 
Furthermore, CNM mutants were seen in association with enlarged clathrin stained 
structures whereas the CMT mutant constructs were associated with clathrin 
structures that appeared clustered, similar to the structures observed in Dnm1 
and Dnm2 double knock-out cells. Other roles of dynamin 2 including its 
interaction with BIN1 (amphiphysin 2), and its function in Golgi maintenance and 
centrosome cohesion were not significantly altered. Taken together, these mild 
functional defects are suggestive of differences between CMT and CNM 
disease-causing dynamin 2 mutants and suggest that a slight impairment in 
clathrin-mediated pathways may accumulate over time to foster the respective 
human diseases.