Novel signaling mechanisms and biological functions induced by the transmembrane protein Lrig1

HITA FRANCISCO J, FERNANDO C. ALSINA, PAULA FONTANET, DOLORES IRALA, FERNANDA LEDDA, GUSTAVO PARATCHA

Córdoba

Congreso; XXVI Reunión Anual de la Sociedad Argentinas de Investigación en Neurociencias 2011; 2011

SOCIEDAD ARGENTINA DE INVESTIGACIÓN EN NEUROCIENCIAS (SAN)

Since discovery of Leucine-rich repeat and Ig-like domain (Lrig) mammalian proteins, they have been characterized as potent inhibitors of many receptor tyrosine kinases, such as Ret, Met and EGFR among others. However, given their structural features, it has been proposed that Lrig transmembrane proteins could influence neuronal development functioning as a cell-type specific adhesion molecule. Here, we show that Lrig1 is able to associate in a homophilic and heterophilic manner, and the presence of the LRR domain is required for these interactions. In neuronal cells expressing endogenous Lrig proteins, the addition of purified Lrig1ECD stimulates axonal growth and promotes the rapid activation of cytoplasmic tyrosine kinases known to participate in cytoeskeletal rearrangements. Together, these results provide an insight into Lrig1 function and establish a new mechanism of intercellular communication with potential relevance for neuronal development.