Reduction of Crk and CrkL expression blocks reelin-induced dendritogenesis

Abstract

The reelin signaling pathway regulates nervous system function after birth, in addition to its role in regulating neuronal positioning during embryogenesis. The receptor-dependent, reelin-induced tyrosine phosphorylation of the Dab1 docking protein is an established prerequisite for biological responses to this ligand. Here we show that the inactivation of a conditional Dab1 allele reduces process complexity in correctly positioned neurons in the CA1 region of the mouse hippocampus after birth. Reelin stimulation of cultured hippocampal neurons enhances dendritogenesis by approximately twofold and in a manner dependent on Src family kinases. This enhancement is blocked by reducing expression of Crk family proteins, adaptor molecules that interact with Dab1 in a tyrosine phosphorylation-dependent manner. Retrovirally expressed inhibitory RNAs used to reduce Crk and CrkL expression did not block BDNF-enhanced dendritogenesis or influence axonogenesis. Together, this demonstrates that the Crk family proteins are important downstream components of the reelin signaling pathway in the regulation of postnatal hippocampal dendritogenesis.

Role of CrkII Signaling in RANKL-Induced Osteoclast Differentiation and Function

“…CrkII and CrkL have overlapping functions in dendritogenesis, phagocytosis, and actin reorganization (24,37,42). In this study, we observed that CrkII and CrkL play a similar role in osteoclasts as in other cell types (Fig.…”

Apolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease

“…Numerous independent studies and observations point toward a role for Reelin and ApoE receptors in the formation of neuronal connections (Del Rio et al 1997;Borrell et al 2007) and the generation of dendritic complexity Costa et al 2001;Niu et al 2004;Matsuki et al 2008;Hoe et al 2009). The latter may, however, not be entirely dependent on Apoer2 and Vldlr (Chameau et al 2009) and may also involve interactions with APP (Hoe et al 2009).…”

Reelin Regulates Postnatal Neurogenesis and Enhances Spine Hypertrophy and Long-Term Potentiation

“…Recently, it has been demonstrated that Reelin participates in the composition, recruitment and traffic of NMDA receptor subunits (Chen et al, 2005;Qiu et al, 2006;Groc et al, 2007), in the generation of dendrites, and in the formation of dendritic spines (Matsuki et al, 2008;Niu et al, 2008). Furthermore, the lack of spines in cultured reeler neurons is recovered by incubation with Reelin (Matsuki et al, 2008;Niu et al, 2008). Altogether, these studies suggest that Reelin is involved in the correct formation and maintenance of synapses.…”

“…Although the role of Reelin in the adult brain is not well understood, it has been shown that this protein is expressed in synaptic contacts, and that neurons deficient in ApoER2 and VLDLR receptors have impaired long-term potentiation (LTP) Beffert et al, 2005). Recently, it has been demonstrated that Reelin participates in the composition, recruitment and traffic of NMDA receptor subunits (Chen et al, 2005;Qiu et al, 2006;Groc et al, 2007), in the generation of dendrites, and in the formation of dendritic spines (Matsuki et al, 2008;Niu et al, 2008). Furthermore, the lack of spines in cultured reeler neurons is recovered by incubation with Reelin (Matsuki et al, 2008;Niu et al, 2008).…”