The question of how cells achieve a high level of spatial organization marks a new frontier in cell biology. Most cells of the human body (e.g., epithelia, neurons) assume asymmetric shapes and develop specialized structures (e.g., cilia, axons, dendrites), which are asymmetrically positioned. Little is known about how cell shape and asymmetry arise from individual molecular interactions. My research lab is investigating the molecular mechanisms that affect spatial organization in epithelia and neurons. We focus on the cytoskeleton, a network of rigid and yet dynamic polymers that sculpt and support cell shape and provide a scaffold for the transport and positioning of the cell’s organelles and macromolecules. We are interested in understanding how cytoskeletal organization and cytoskeleton-dependent transport are spatially regulated. We have gained new insights into this problem by studying a family of GTP-binding proteins termed septins, which associate with the cytoskeleton and cell membranes. Unlike the monomeric small GTPases, septins polymerize into higher order filamentous structures that scaffold and restrict protein localization in the cytoplasm and cell membranes. We have discovered that septins demarcate spatially distinct regions of the cytoplasm, interacting with distinct subsets of microtubules and actin filaments. Importantly, we have found that septins are required for the generation of epithelial and neuronal cell asymmetry and the spatial organization of a variety of cell processes (e.g., cell division and motility) and structures (e.g., axon branches, primary cilia). We hypothesize that septins are key regulators of spatial organization and investigate the molecular mechanisms underlying the regulatory functions of septins.
