title: High-content analysis of proapoptotic EphA4 dependence receptor functions using small-molecule libraries.
abstract: Small-molecule compounds (SMCs) can provide an inexpensive and selective approach to modifying biological responses. High-content analysis (HCA) of SMC libraries can help identify candidate molecules that inhibit or activate cellular responses. In particular, regulation of cell death has important implications for many pathological conditions. Dependence receptors are a new classification of proapoptotic membrane receptors that, unlike classic death receptors, initiate apoptotic signals in the absence of their ligands. EphA4 has recently been identified as a dependence receptor that may have important functions in conditions as disparate as cancer biology and CNS injury and disease. To screen potential candidate SMCs that inhibit or activate EphA4-induced cell death, HCA of an SMC library was performed using stable EphA4-expressing NIH 3T3 cells. Our results describe a high-content method for screening dependence receptor-signaling pathways and demonstrate that several candidate SMCs can inhibit EphA4-mediated cell death.
authors.affiliation: The Miami Project to Cure Paralysis and Department of Neurosurgery, University of Miami School of Medicine, Miami, FL 33136, USA.
authors.forename: Claudiu M
authors.initials: CM
authors.lastname: Nelersa
authors.forename: Henry
authors.initials: H
authors.lastname: Barreras
authors.forename: Erik
authors.initials: E
authors.lastname: Runko
authors.forename: Jerome
authors.initials: J
authors.lastname: Ricard
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Glass
authors.forename: John L
authors.initials: JL
authors.lastname: Bixby
authors.forename: Vance P
authors.initials: VP
authors.lastname: Lemmon
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Liebl
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D036342:Ephrins / Q000378:metabolism; D005456:Fluorescent Dyes; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D036122:Receptor, EphA4 / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000235:genetics; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D036342:Ephrins; D005456:Fluorescent Dyes; D054852:Small Molecule Libraries; D036122:Receptor, EphA4