Telephone: (301) 496-2898

E-mail: danielsm@nhlbi.nih.gov 

Office: Building 50, Room 3318

• Differentiation of nerve and muscle cells, organization of excitable membranes.
• Synapse formation, maintenance and remodeling in the central and peripheral nervous system.

My laboratory studies the differentiation of neurons and skeletal muscle cells. Our research has emphasized the development of the vertebrate neuromuscular junction, the synapse that triggers skeletal muscle contraction. Agrin is a proteoglycan with a multifunctional protein backbone that is secreted by motor neurons. It is an essential signal for postsynaptic differentiation of the neuromuscular junction during embryonic development. We recently demonstrated that agrin secretion is targeted to the axons of embryonic motor neurons in culture. Current projects focus on the mechanisms of targeting, transport and secretion of agrin by these neurons. Full-length and truncated recombinant agrins fused with fluorescent proteins are expressed in cultured rat motor neurons by transfection with plasmid DNAs or infection with viral vectors. The trafficking of these recombinant agrins is analyzed by fluorescence microscopy and compared to that of other neuronal proteins such as synaptic vesicle proteins. By these approaches we are identifying the portions of the agrin molecule involved in targeting and secretion and characterizing the intracellular compartment in which agrin is transported. 

In addition to the secreted form of agrin expressed by motor neurons, a transmembrane form with a different amino terminus is widely expressed in neurons of the central nervous system. Possible functions of this form of agrin include regulation of neuron outgrowth, synapse formation and postsynaptic excitation. We are currently investigating novel functions of transmembrane agrin by studying the effects of altering its expression in cultured neurons and other cells types.