Unknown

Dataset Information

0

Dynamin triple knockout cells reveal off target effects of commonly used dynamin inhibitors.


ABSTRACT: Dynamin, which is encoded by three genes in mammals, is a GTPase implicated in endocytic membrane fission. Dynamin 1 and 3 are predominantly expressed in brain, whereas dynamin 2 is ubiquitously expressed. With the goal of assessing the impact of the lack of dynamin on cell physiology, we previously generated and characterized dynamin 1 and 2 double knockout (DKO) fibroblasts. These DKO cells were unexpectedly viable in spite of a severe impairment of clathrin-mediated endocytosis. As low-level expression of the dynamin 3 gene in these cells could not be excluded, we have now engineered dynamin 1, 2 and 3 triple KO (TKO) fibroblasts. These cells did not reveal any additional defects beyond what was previously observed in DKO fibroblasts. Surprisingly, although fluid-phase endocytosis and peripheral membrane ruffling were not impaired by the lack of all three dynamins, two structurally similar, widely used dynamin inhibitors, dynasore and Dyngo-4a, robustly inhibited these two processes both in wild-type and TKO cells. Dynamin TKO cells will be useful tools for the further exploration of dynamin-dependent processes and the development of more specific dynamin inhibitors.

SUBMITTER: Park RJ 

PROVIDER: S-EPMC3828596 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Dynamin triple knockout cells reveal off target effects of commonly used dynamin inhibitors.

Park Ryan J RJ   Shen Hongying H   Liu Lijuan L   Liu Xinran X   Ferguson Shawn M SM   De Camilli Pietro P  

Journal of cell science 20130917 Pt 22


Dynamin, which is encoded by three genes in mammals, is a GTPase implicated in endocytic membrane fission. Dynamin 1 and 3 are predominantly expressed in brain, whereas dynamin 2 is ubiquitously expressed. With the goal of assessing the impact of the lack of dynamin on cell physiology, we previously generated and characterized dynamin 1 and 2 double knockout (DKO) fibroblasts. These DKO cells were unexpectedly viable in spite of a severe impairment of clathrin-mediated endocytosis. As low-level  ...[more]

Similar Datasets

| S-EPMC5523961 | biostudies-literature
| S-EPMC2984188 | biostudies-literature
| S-EPMC1221339 | biostudies-other
| S-EPMC4411397 | biostudies-literature
| S-EPMC2144310 | biostudies-other
| S-EPMC10538457 | biostudies-literature
| S-EPMC3170251 | biostudies-literature
| S-EPMC3659109 | biostudies-literature
| S-EPMC8145957 | biostudies-literature
| S-EPMC3890566 | biostudies-literature