Among the host of proteins performing specialized tasks within our cells is dynamin, which acts like molecular scissors to cut and remodel the cell’s internal membranes. This protein is part of a family of molecular machines that use chemical energy to change shape and perform work. These functions enable cells to interact with their environment and maintain their internal organization.
Dynamin’s Role in Cellular ‘Pinching’
One of dynamin’s most understood functions is its role in endocytosis, the process by which cells internalize substances. This mechanism allows cells to absorb nutrients, regulate signals, and manage the composition of their plasma membrane. During endocytosis, a section of the plasma membrane folds inward, creating a pocket that engulfs material and deepens into a bud connected to the surface by a narrow neck.
This is where dynamin performs its signature ‘pinching’ action. Molecules of dynamin assemble into a ring-like spiral around the membrane neck. Once assembled, the dynamin ring constricts, squeezing the membrane neck until it breaks and releases the newly formed vesicle into the cell’s interior.
Without this pinching function, endocytosis would stall. The membrane pockets would form but be unable to detach from the plasma membrane. This would trap them at the cell surface, preventing the cell from taking in materials necessary for its survival.
The Mechanics of Dynamin Action
Dynamin’s ability to sever membranes is powered by its function as a GTPase, an enzyme that binds and hydrolyzes guanosine triphosphate (GTP). This process releases energy, which dynamin converts into mechanical force. The protein has a distinct structure with several domains, including a GTP-binding domain, a middle domain, and a GTPase effector domain (GED), which work together to achieve membrane fission. The cycle of GTP binding and hydrolysis drives conformational changes in the dynamin protein.
Dynamin molecules self-assemble into a helical collar around the neck of a budding vesicle. This assembly brings multiple GTPase domains into close proximity, stimulating their enzymatic activity. Once the spiral is in place, the hydrolysis of GTP triggers a significant structural change, described by the “constrictase” model where the helix tightens its grip around the membrane tubule, like tightening a drawstring bag.
This constriction squeezes the membrane neck, generating the force needed for fission. An alternative idea, the “poppase” model, suggests that structural changes from GTP hydrolysis create tension in the helix, leading to its disassembly and the snapping of the membrane. In either model, the conversion of chemical energy from GTP into mechanical work is the central principle.
Beyond Pinched Vesicles: Dynamin’s Other Jobs
While dynamin is best known for vesicle formation at the plasma membrane, its membrane-remodeling capabilities are used in other cellular locations. The ability to constrict and sever membrane tubules is a versatile tool the cell employs for maintaining the structure of its internal organelles.
One role for dynamin-like proteins is in the maintenance of mitochondria, the cell’s powerhouses. These organelles constantly undergo cycles of division (fission) and merging (fusion). A dynamin-related protein called Drp1 assembles on the outer mitochondrial membrane to mediate fission, ensuring damaged parts can be removed and mitochondria can be segregated during cell division.
Dynamin is also involved in trafficking vesicles from the Golgi apparatus, a central sorting station in the cell. Dynamin-2 facilitates the scission of these transport vesicles, which carry proteins and lipids to other destinations. Dynamin also contributes to processes like cytokinesis, the final step of cell division, and phagocytosis, the engulfment of large particles.
Meet the Dynamin Family
The term “dynamin” refers to a superfamily of related proteins that share a common mechanical principle. This diverse family of large GTPases participates in a wide range of membrane remodeling events across different cellular compartments. They possess distinct features that target them to specific locations and tasks.
In mammals, the classical dynamins and related proteins include:
- Dynamin-1: Predominantly found in neurons, it is involved in the rapid recycling of synaptic vesicles for nerve communication.
- Dynamin-2: Expressed in most cell types, it is the primary form involved in the common clathrin-mediated endocytosis pathway.
- Dynamin-3: Concentrated in nervous tissue, it has specialized roles in the postsynaptic terminals of neurons.
- Drp1: This dynamin-related protein is responsible for mitochondrial fission.
- Mitofusins and OPA1: In contrast to Drp1, these proteins mediate mitochondrial fusion.
- Mx proteins: These are induced by interferons and have antiviral properties, demonstrating the functional diversification of this protein group.
When Dynamin Goes Wrong: Health Implications
Given the widespread roles of dynamin proteins, mutations in the genes that code for them can lead to serious human diseases. When dynamin’s ability to remodel membranes is compromised, processes ranging from nerve signaling to muscle maintenance can be disrupted.
Mutations in the DNM2 gene, which codes for Dynamin-2, are linked to two distinct neuromuscular disorders. One is a form of Charcot-Marie-Tooth (CMT) disease, a peripheral neuropathy characterized by muscle weakness and atrophy. The other is centronuclear myopathy (CNM), a condition that affects skeletal muscles, leading to weakness and developmental delays. The specific location of the mutation appears to determine whether the nerves or the muscles are primarily affected.
The cellular consequences of these mutations often relate to altered GTPase activity or self-assembly. Some mutations cause Dynamin-2 to become hyperactive, leading to excessive membrane fission and fragmentation of cellular structures in muscle cells, as seen in CNM. Other mutations may impair dynamin’s function, disrupting endocytosis and other trafficking events important for the health of long peripheral nerves in CMT.