Poster abstracts

Poster number 98 submitted by Daisy Alvarado

Analysis of Adhesive Interactions in Isoforms of Cadherins Relevant for Lung Function and Hearing.

Daisy Alvarado (Biophysics ), Debadita Modak (Chemistry and Biochemistry )

Abstract:
The cadherin superfamily of calcium-dependent adhesion proteins has of over 100 members in the human genome. The biological function and biophysical properties of various members of the superfamily have been extensively studied in vivo and in vitro but understanding how alternative splicing alters their function remains unexplored in most cases. Here we have focused on two distinct non-clustered protocadherins that play a crucial role in cell-cell adhesion and sensory transduction and that have various isoforms resulting from gene splicing. The non-clustered Homo Sapiens (hs)protocadherin-1(PCDH1) is involved in respiratory function and it has an ectodomain composed of seven extracellular cadherin (EC) “repeats” that can mediate a trans (across cell membranes) adhesive bond formed by EC1-4 monomers arranged in an overlapped antiparallel complex. Intriguingly, hs PCDH1 has an isoform of unknown function that lacks the EC1-3 fragments. Likewise, the non-clustered Mus musculus (mm) cadherin-23 (CDH23) essential for hearing has an extracellular domain with 27 EC repeats and one of its isoforms lacks its adhesive repeats EC1-2 and most of the ectodomain. Here we have focused on testing the adhesive function of these two isoforms by producing C-terminal Fc tagged hsPCDH1 EC4-7 and mm CDH23 EC21-MAD28 protein fragments in HEK293 cells. Protein G beads were mixed with these fragments and used to investigate homophilic adhesion interactions, which were not observed. The biological function of these isoforms remains to be established.

Keywords: Protocadherins