GPR56/ADGRG1 is an adhesion GPCR and mutations on this receptor cause cortical malformation due to the over-migration of neural progenitor cells on the brain surface. At the pial surface, GPR56 interacts with collagen III, induces Rho dependent activation through Gα12/13 and inhibits the neuronal migration. In human glioma cells, GPR56 inhibits cell migration through Gαq/11 dependent Rho pathway. GPR56-tetraspanin complex is known to couple with Gαq/11. GPR56 is an aGPCR that couples with various G proteins and signals through different downstream pathways. In this study, BFPP mutants disrupting GPR56 function but remain to be expressed on plasma membrane were used to study receptor signaling through Gα12, Gα13 and Gα11 with BRET biosensors. GPR56 showed coupling with all three G proteins and activated heterotrimeric G protein signaling upon stimulation with Stachel peptide. However, BFPP mutants showed different signaling defects for each G protein indicative of distinct activation and signaling properties of GPR56 for Gα12, Gα13 or Gα11. β-arrestin recruitment was also investigated following the activation of GPR56 with Stachel peptide using BRET biosensors. N-terminally truncated GPR56 showed enhanced β-arrestin recruitment, however neither wild-type receptor nor BFPP mutants gave any measurable recruitment upon Stachel stimulation, pointing different activation mechanisms for β-arrestin involvement.

This study presents the comparative cell attachment investigation of TAT and well-known RGD peptide modified surfaces.

GPR56/ADGRG1 is an adhesion G protein‐coupled receptor (GPCR) and mutations on this receptor cause cortical malformation due to the over‐migration of neural progenitor cells on brain surface. At pial surface, GPR56 interacts with collagen III, induces Rho‐dependent activation through Gα12/13 and inhibits the neuronal migration. In human glioma cells, GPR56 inhibits cell migration through Gαq/11‐dependent Rho pathway. GPR56‐tetraspanin complex is known to couple Gαq/11. GPR56 is an aGPCR that couples with various G proteins and signals through different downstream pathways. In this study, bilateral frontoparietal polymicrogyria (BFPP) mutants disrupting GPR56 function but remaining to be expressed on plasma membrane were used to study receptor signalling through Gα12, Gα13 and Gα11 with BRET biosensors. GPR56 showed coupling with all three G proteins and activated heterotrimeric G protein signalling upon stimulation with Stachel peptide. However, BFPP mutants showed different signalling defects for each G protein indicative of distinct activation and signalling properties of GPR56 for Gα12, Gα13 or Gα11. β‐arrestin recruitment was also investigated following the activation of GPR56 with Stachel peptide using BRET biosensors. N‐terminally truncated GPR56 showed enhanced β‐arrestin recruitment; however, neither wild‐type receptor nor BFPP mutants gave any measurable recruitment upon Stachel stimulation, pointing different activation mechanisms for β‐arrestin involvement.

Peptide therapeutics are robust and promising molecules for treating diverse disease conditions. These molecules can be developed from naturally occurring or mimicking native peptides, through rational design and peptide libraries. We developed a new platform for the rapid screening of the peptide therapeutics for disease targets. In the course of the study, we aimed to employ our platform to screen a new generation of peptide therapeutics candidates against aggregation prone protein targets. Two peptide drug candidates for the protein aggregation prone diseases namely Parkinson s and Alzheimer s diseases were screened. Currently, there are several therapeutic applications that are only effective in masking or slowing down symptom development. Nonetheless, different approaches are developed for inhibiting amyloid aggregation in the secondary nucleation phase, which is critical for amyloid fibril formation. Instead of targeting secondary nucleated protein structures, we tried to inhibit monomeric amyloid units as a novel approach for halting disease-condition. To achieve this, we combined yeast surface display and phage display library platforms. We expressed alpha-synuclein, amyloid beta 40 and amyloid beta 42 on yeast surface, and we selected peptides by using phage display library. After iterative biopanning cycles optimized for yeast cells, several peptides were selected for interaction studies. All of the peptides have been used in vitro characterization methods which are QCM-D measurement, AFM imaging, and ThT assay, and they have yielded promising results in order to block fibrillization or interact with amyloid units as a sensor molecule candidate. Therefore, peptides are good choice for diverse disease-prone molecule inhibition particularly those inhibiting fibrillization. Additionally, these selected peptides can be used as drugs and sensors to detect disease quickly and halt disease progression.