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In-Depth Information
like its binding partner Homer, Dyn3 may function to help regulate the
dendritic maturation process, causing the growth of filopodia that will
eventually stabilize as spines. As the overexpression of either Homer or Dyn3
have opposite effects on spine morphology, perhaps a balance between the
activities of each protein is necessary to allow for proper development to
occur.
Future studies will explore the role of Dyn3 during the regulation of the
filopodia/spine actin cytoskeleton. The effects of Dyn3 expression on spine
morphogenesis outlined above may involve actin, as Dyn3-induced neuronal
filopodia are lost following treatment with the actin depolymerizing drug
Latrunculin A (N.W.G. and M.A.M., unpublished data). Preliminary data
also suggest that, like Dyn2, Dyn3 binds to cortactin, an interaction that could
modulate the rate and extent of actin polymerization and branching. As Dyn2
was recently found to stimulate actin polymerization, in conjunction with
cortactin and other actin-binding proteins (Schafer et al., 2002), there is a
precedent warranting the examination of Dyn3 as a potential actin
cytoskeleton modulator in neurons.
Conclusions and perspectives
Here we have provided a short discussion of dynamin and some actin-
membrane-dependent processes in which this mechanoenzyme has been
shown to function. Additional cellular processes that may apply to the study
of the dynamin-actin-membrane interface include growth cone extension,
immunological synapse formation and cell adhesion. How does dynamin
mediate these processes? The current data develop a hypothesis in which
dynamin is recruited to the actin-membrane interface via its PH domain and
PRD, where it associates with phospholipids and cytoskeletal proteins to
regulate various cell processes. In the case of vesicle formation, dynamin is
recruited to the invaginated vesicles where it constricts the membrane neck
and, through its interactions with actin nucleation proteins, stimulates a
'burst' of F-actin nucleation. This new actin polymerization results in the
severing or 'breaking' of the vesicle neck, liberating it from its donor
membrane. However, in non-vesicle forming processes, such as membrane
ru
ing, cytokinesis and dendritic spine morphogenesis, dynamin's role is less
clear and, despite recent advances, needs to be studied further. Several
important questions about dynamin's role in cytoskeletal processes remain
enigmatic. For example, how are dynamin's interactions with binding partners
regulated in time and space? What is the function of dynamin in these
complexes? How does a mechanochemical motor, dynamin, mediate the
polymerization, stability and organization of microfilaments? Further, it will
be important to study the roles of the many spliced-forms of dynamin during
