ErbB4 is a tyrosine kinase receptor whose activity can be finely regulated by two different alternative splicing, producing isoforms susceptible or not to ectodomain shedding and endowed or not with a phosphatydilinositol-3-kinase binding domain. We previously cloned and expressed the four ErbB4 isoforms in the neural progenitor cell line ST14A (already expressing ErbB1, ErbB2, and ErbB3), and showed that these cells, although with different intensity, acquire the ability to migrate following stimulation with soluble neuregulin-1-beta-1. It has been suggested that the different soluble and transmembrane isoforms of neuregulin-1 can act as short- and long-range attractants for migration of cortical and olfactory interneurons expressing ErbB4. Therefore, we focused our attention at studying juxtacrine interactions between cells expressing one out of the four ErbB4 isoforms and cells expressing a transmembrane (and cleavable) isoform of neuregulin-1. We subcloned and stably expressed neuregulin-1-typeIII-beta-3 in the neural progenitor cell line ST14A, obtaining cells expressing a transmembrane neuregulin susceptible to ectodomain shedding, accordingly to literature data. These cells are potentially able to interact paracrinely by releasing the soluble fragment containing the receptor binding domain, juxtacrinely by interacting with other cells through the full length transmembrane isoform. By stripe choice assay, we show that cells expressing different ErbB4 isoforms prefer to adhere on substrates expressing neuregulin-1-typeIII and that the four ErbB4 isoforms show some different adhesion preferences. Financial support from MIUR (FIRB RBAU01BJ95) and Regione Piemonte (Prog. Ric. San. Fin. 2004, Prog DIADI “Tesina” 2003-2006).
Analysis of juxtacrine interactions mediated by ErbB4 and neuregulin-1-typeIII
GAMBAROTTA, Giovanna;FREGNAN, Federica;FASOLO, Aldo;PERROTEAU, Isabelle
2006-01-01
Abstract
ErbB4 is a tyrosine kinase receptor whose activity can be finely regulated by two different alternative splicing, producing isoforms susceptible or not to ectodomain shedding and endowed or not with a phosphatydilinositol-3-kinase binding domain. We previously cloned and expressed the four ErbB4 isoforms in the neural progenitor cell line ST14A (already expressing ErbB1, ErbB2, and ErbB3), and showed that these cells, although with different intensity, acquire the ability to migrate following stimulation with soluble neuregulin-1-beta-1. It has been suggested that the different soluble and transmembrane isoforms of neuregulin-1 can act as short- and long-range attractants for migration of cortical and olfactory interneurons expressing ErbB4. Therefore, we focused our attention at studying juxtacrine interactions between cells expressing one out of the four ErbB4 isoforms and cells expressing a transmembrane (and cleavable) isoform of neuregulin-1. We subcloned and stably expressed neuregulin-1-typeIII-beta-3 in the neural progenitor cell line ST14A, obtaining cells expressing a transmembrane neuregulin susceptible to ectodomain shedding, accordingly to literature data. These cells are potentially able to interact paracrinely by releasing the soluble fragment containing the receptor binding domain, juxtacrinely by interacting with other cells through the full length transmembrane isoform. By stripe choice assay, we show that cells expressing different ErbB4 isoforms prefer to adhere on substrates expressing neuregulin-1-typeIII and that the four ErbB4 isoforms show some different adhesion preferences. Financial support from MIUR (FIRB RBAU01BJ95) and Regione Piemonte (Prog. Ric. San. Fin. 2004, Prog DIADI “Tesina” 2003-2006).
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