Daniel Suter
Daniel Suter
Assistant Professor; Ph.D., University of Zurich, 1995

The human brain contains about 1011 neurons; each of them can have 103 connections to other neurons. The establishment of specific connections within the nervous system that result in functional processing units appears to be a very complex and difficult task. A key player in making the appropriate connections during development and regeneration of the nervous system is the neuronal growth cone, a sophisticated structure located at the end of neuronal processes and capable of integrating sensor, signaling and motility functions.

Our laboratory is interested to study how growth cones achieve such integration. Recent genetics and genomics efforts have identified a large number of proteins that may be involved in growth cone motility and guidance; however, their detailed locations, dynamics and functions on the cellular level remain mostly unknown. Specifically, we would like to understand how extracellular signals, such as from cell adhesion molecules, are transduced inside the cell to affect the underlying cytoskeletal structures and dynamics; these changes ultimately determine speed and direction of the growth cone. To address this problem, we use a combination of advanced live cell imaging techniques, biophysical methods such as laser tweezers and micromanipulations, and molecular techniques. These methods allow us to investigate the dynamics and functions of adhesion, signaling, and cytoskeletal proteins, and to analyze cellular forces.

Our favorite experimental system currently are cultured neurons from Aplysia californica, because they have large growth cones enabling studies of cell motility, cytoskeletal protein dynamics and cellular forces at a high resolution in space and time. Using a novel growth cone steering assay (see Figure), we have previously shown that the immunoglobulin superfamily cell adhesion molecule apCAM can act as a coupling agent, transducing force between extracellular substrates and intracellular actomyosin networks. Further studies revealed a role for a Src family tyrosine kinase in the regulation of this substrate-cytoskeletal coupling mechanism. More recently, we have been working on the role of microtubule extension in growth cone steering events. One of our future research efforts aims at a more detailed molecular and biophysical analysis of the apCAM-F-actin coupling complex. We are also very interested to test the coupling hypothesis in different cell adhesion systems as well as in other motile cells.

Figure: Aplysia growth cone steering event induced by a silica bead coated with an antibody against the cell surface protein apCAM and restrained with a microneedle against retrograde translocation. Left panel: DIC image taken at start of the experiment; middle panel: central domain extended towards the restrained bead; right panel: F-actin (red) accumulated at and microtubules (green) extended towards the target side.

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