Imperial College London


Faculty of MedicineDepartment of Brain Sciences

Professor of Neurology and Genomic Medicine



m.johnson Website




E419Burlington DanesHammersmith Campus






BibTex format

author = {Dhindsa, RS and Bradrick, SS and Yao, X and Heinzen, EL and Petrovski, S and Krueger, BJ and Johnson, MR and Frankel, WN and Petrou, S and Boumil, RM and Goldstein, DB},
doi = {10.1212/01.NXG.0000464295.65736.da},
journal = {Neurology: Genetics},
title = {Epileptic encephalopathy-causing mutations in DNM1 impair synaptic vesicle endocytosis},
url = {},
volume = {1},
year = {2015}

RIS format (EndNote, RefMan)

AB - OBJECTIVE: To elucidate the functional consequences of epileptic encephalopathy-causing de novo mutations in DNM1 (A177P, K206N, G359A), which encodes a large mechanochemical GTPase essential for neuronal synaptic vesicle endocytosis. METHODS: HeLa and COS-7 cells transfected with wild-type and mutant DNM1 constructs were used for transferrin assays, high-content imaging, colocalization studies, Western blotting, and electron microscopy (EM). EM was also conducted on the brain sections of mice harboring a middle-domain Dnm1 mutation (Dnm1 (Ftfl)). RESULTS: We demonstrate that the expression of each mutant protein decreased endocytosis activity in a dominant-negative manner. One of the G-domain mutations, K206N, decreased protein levels. The G359A mutation, which occurs in the middle domain, disrupted higher-order DNM1 oligomerization. EM of mutant DNM1-transfected HeLa cells and of the Dnm1 (Ftfl) mouse brain revealed vesicle defects, indicating that the mutations likely interfere with DNM1's vesicle scission activity. CONCLUSION: Together, these data suggest that the dysfunction of vesicle scission during synaptic vesicle endocytosis can lead to serious early-onset epilepsies.
AU - Dhindsa,RS
AU - Bradrick,SS
AU - Yao,X
AU - Heinzen,EL
AU - Petrovski,S
AU - Krueger,BJ
AU - Johnson,MR
AU - Frankel,WN
AU - Petrou,S
AU - Boumil,RM
AU - Goldstein,DB
DO - 10.1212/01.NXG.0000464295.65736.da
PY - 2015///
SN - 2376-7839
TI - Epileptic encephalopathy-causing mutations in DNM1 impair synaptic vesicle endocytosis
T2 - Neurology: Genetics
UR -
UR -
VL - 1
ER -