"Gearing" up for dynamin-catalyzed membrane fission

Area of Science:

• Biochemistry
• Cell Biology
• Molecular Biology

Background:

• Endocytic dynamins are GTPases that form helical scaffolds.
• They constrict and sever tubular membrane necks during endocytosis.
• Membrane binding involves the pleckstrin-homology domain (PHD).

Purpose of the Study:

• To review current understanding of dynamin-catalyzed membrane fission.
• To reconcile contrasting biochemical and cellular findings on the PHD's role.
• To propose a model for PHD function in dynamin catalysis.

Main Methods:

• Review of existing biochemical and cellular studies.
• Analysis of structure-function relationships of dynamin's PHD.
• Integration of data to propose a mechanistic model.

Main Results:

• The PHD has four unstructured loops, with two inserting into the membrane.
• Membrane insertion by these loops reduces membrane bending rigidity.
• Mutations in these loops have distinct effects on fission efficiency.

Conclusions:

• The two membrane-inserting loops of the PHD function as "gears".
• These loops regulate the catalytic efficiency of the dynamin scaffold.
• This mechanism reconciles diverse observations on dynamin-mediated membrane fission.