Chan Thu (Columbia U)

Chan Thu (Columbia U)

Special Seminar

Event Date/Location

January 20, 2016 - 12:00 pm

Speaker

  • Photo of Chang Thu

    Chan Thu

    Department of Biochemistry and Molecular Biophysics
    Columbia University

Topic

Molecular mechanisms of neuronal self-recognition mediated by the clustered protocadherins

A key principle of neural circuit assembly is neurite self-avoidance, whereby sister axons or dendrites of the same neuron repel each other. This process is necessary to achieve efficient coverage of projection or receptive fields. Remarkably, however, sister neurites engaged is self-avoidance interact freely with other neurons, indicating that   neurons can discriminate “self” from “non-self”. Self-identity of neuron is determined by stochastic expression of a distinct set of cadherin superfamily members called clustered protocadherin (Pcdh) α, β and γ proteins in mammals.

In order to better understand to role of individual Pcdh isoforms in generating single cell diversity, we have carried out detailed functional and structural studies of the clustered Pcdhs (in collaboration with the groups of Larry Shapiro and Barry Honig at Columbia). Using a cell aggregation assay for homophilic interactions of distinct Pcdh isoforms, we have found that individual Pcdh α, β and γ protein isoforms exhibit strict homophilic binding, and that multiple distinct Pcdh isoforms can act combinatorially to generate unique multi- isoform trans binding specificities. Based on our findings from X-ray 3D structures and computational studies, we proposed that sister neurites from the same neuron can form a large assembly or lattice of Pcdh units through specific homophilic interactions. In contrast, non-sister neurites displaying different Pcdh isoform compositions would incorporate mismatches, preventing the formation of the lattice.  Thus, the size of Pcdh complexes or lattice at the site of contacts may determine the strength of downstream signaling leading to neurite repulsion in vivo. Our detailed structure studies provide the molecular nature of Pcdh homophilic interactions and the mechanisms by which the clustered Pcdhs provide individual neurons with a unique cell surface identity.

Audience

Free and open to the university community and the public

Host

Elizabeth Gavis, Department of Molecular Biology