Among the countless proteins that maintain cellular function is dynamin, a molecular machine that acts as a GTPase. This class of proteins binds and hydrolyzes guanosine triphosphate (GTP) to power their work. Dynamin’s ability to remodel cellular membranes makes it a participant in processes ranging from nutrient uptake to cell division. Its activities in shaping and transporting cellular components underscore its importance in maintaining the health of eukaryotic cells. The protein’s versatility makes it a subject of extensive scientific study.
The Role of Dynamin in Endocytosis
One of the most well-documented roles for dynamin is in endocytosis. This is how cells import substances from their external environment, including nutrients and signaling molecules. During endocytosis, the cell’s outer membrane folds inward to create a pocket around the targeted material. This budding vesicle must then be pinched off from the membrane to become a free-floating container. This step of membrane fission is where dynamin performs its signature function.
Dynamin molecules are recruited to the neck of this newly forming vesicle. There, they assemble into a helical collar that wraps tightly around the membrane stalk connecting the vesicle to the cell surface. This structure acts like a molecular drawstring. By constricting this collar, dynamin generates the mechanical force needed to sever the membrane, releasing the vesicle into the cell. Without this action, the process of bringing materials into the cell would fail.
This function is not limited to one type of endocytosis. Dynamin is involved in clathrin-mediated endocytosis, a major pathway for receptor internalization, but it also participates in other, clathrin-independent pathways. For instance, it is involved in caveolae internalization. The protein’s involvement in synaptic vesicle recycling in nerve cells highlights its importance in neuronal communication, where rapid internalization of neurotransmitters is necessary for continuous signaling.
How Dynamin Works
The mechanical action of dynamin is powered by its identity as a GTPase, an enzyme that harnesses energy from guanosine triphosphate (GTP). This process is an example of how cells convert chemical energy into physical force. The mechanism begins with the recruitment and assembly of individual dynamin proteins at the site of membrane fission. These proteins are drawn to the neck of a budding vesicle, where they link together.
Once at the membrane neck, dynamin molecules self-assemble into a helical polymer, forming a tight collar structure. This assembly is a regulated step, influenced by other proteins and the lipid composition of the membrane itself. The structure of this dynamin collar is dynamic. The binding of GTP molecules to the GTPase domains of the assembled dynamin proteins sets the stage for the next event.
The key action is GTP hydrolysis, the process where GTP is broken down into guanosine diphosphate (GDP) and a phosphate group. This chemical reaction releases energy, which drives a significant conformational change in the dynamin proteins. This shape change causes the helical collar to constrict powerfully. This constriction squeezes the underlying membrane tube, leading to its scission and the release of the vesicle. The dynamin collar then disassembles, and the proteins are recycled.
Dynamin’s Diverse Cellular Roles
Beyond its well-known function in pinching off vesicles, dynamin’s responsibilities extend to several other cellular activities. Its ability to manipulate membranes makes it a versatile tool used in various contexts:
- Mitochondrial dynamics: Dynamin-related proteins are required to sculpt the membranes of mitochondria as they constantly undergo fission (division) and fusion (merging).
- Cytokinesis: In the final stage of cell division, dynamin is recruited to the cleavage furrow to contribute to the membrane remodeling needed for the separation of daughter cells.
- Golgi trafficking: It assists in forming transport vesicles that bud from the Golgi apparatus, which sorts and packages proteins and lipids for delivery to other destinations.
- Cell adhesion and migration: Dynamin is involved in the formation of specialized cellular structures like podosomes, which are involved in cell adhesion and migration.
The Consequences of Dynamin Dysfunction
Given dynamin’s widespread roles, malfunctions in this protein can have significant consequences for human health. Mutations in the genes that provide instructions for making dynamin proteins, particularly the DNM2 gene, are linked to several inherited diseases. These conditions often affect tissues highly dependent on dynamin-regulated processes, such as the nervous system and skeletal muscles.
One example is Charcot-Marie-Tooth (CMT) disease, a group of inherited disorders that damage peripheral nerves. Certain mutations in DNM2 cause specific forms of CMT, leading to symptoms like muscle weakness and atrophy, and sensory loss. The nerve damage in CMT is thought to arise from defects in membrane trafficking within neurons and the Schwann cells that myelinate them.
Another condition caused by DNM2 mutations is centronuclear myopathy (CNM), a disorder characterized by muscle weakness and misplaced nuclei within muscle fibers. In CNM, the mutated dynamin protein can interfere with membrane structures inside muscle cells important for muscle contraction. The different locations of mutations within the DNM2 gene can lead to either CMT or CNM, highlighting how specific changes to the protein’s structure result in distinct pathologies.