A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones

Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-of-function experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

The experience of identity transformation process for people living with tetraplegia and paraplegia = El proceso de reconstrucción de la identidad de las personas afectadas de una paraplejia o tetraplejia

A spinal cord injury (SCI) is perceived as a source of biographical disruption, not only at a physical level but also in terms of people’s life stories, their motivation and their self-esteem. The aim of this study is to explore the factors that people with spinal cord injuries perceive as contributing to rebuilding their sense of self. Two focus groups were established from the SCIcommunity, one of which was made up of 14 people with paraplegia and the other of 9 people with tetraplegia. In addition, four individual interviews were conducted with the participants. The results of content analysis show that the two most prominent factors in the process of identity renegotiation are the partial transformation of the subject’s identity followed by a coming to terms with that new identity. To rebuild self-worth, the importance of finding a balance between change and continuity was identified. Renegotiation of identity after a spinal cord injury is a complex phenomenon that greatly influences the SCI individual’s quality of life perceptions. Reaching a balance between the changes experienced due to the injury and finding a sense of continuity can be either facilitated or obstructed by the economic, political, legal, architectural, and social context

Actuación interdisciplinar en alteraciones por espina bífida en el pie

La malformación congénita conocida como Espina Bífida se caracteriza por la ausencia de fusión de la línea media posterior de la columna vertebral produciéndose una hernia del contenido del conducto vertebral (médula, meninges y raíces nerviosas). Este síndrome compromete múltiples sistemas del organismo, debiéndose tratar por un equipo multidisciplinar. A nivel del pie se producen deformidades tanto flácidas como espásticas con déficit motores radiculares (55%). Estos problemas estructurales provocaran alteraciones biomecánicas severas con sobrecargas a nivel plantar (33%). Si a esto añadimos alteraciones radiculares sensitivas, con insensibilidad en piernas y pies (60%), nos encontramos ante un paciente de riesgo susceptible de tratamientos preventivos y curativos podológicos. Las probabilidades de padecer una úlcera neuropática son grandes y el Podólogo debe prevenir o, en el peor de los casos, tratar el mal perforante plantar de una forma interdisciplinar. Preventivamente realizaremos quiropodias periódicas y exploración de sensibilidades, tanto exteroceptivas como propioceptivas. A nivel podológico trataremos de una forma integral la úlcera neuropática, incluyendo los drenajes y las"toilettes" quirúrgicas, y realizaremos tratamientos ortopodológicos complejos. En esta comunicación presentamos un caso típico de paciente afecto de Espina Bífida con alteraciones biomecánicas severas y úlcera con recorrido fistuloso, al cual realizamos un drenaje y confeccionamos una férula supramaleolar interna unilateral para redistribuir las presiones y evitar las sobrecargas.