◈ Topic : A role of novel glycoprotein NELL2 in glutamatergic neuron and female sexual development
◈ Speaker : Pro. chang man Ha (College of Medicine, Yonsei University)
◈ Date/Time : 2:00/Jan.7/2010
◈ Place : POSTECH Biotech Center
◈ Information : Pro. Pann-Ghill Suh (279-2293)
◈ Abstract
NELL2, a protein containing EGF-like repeats, is almost exclusively expressed in the nervous system. NELL2 was previously found to be a secreted protein that functions during embryonic development as a neuronal differentiation and survival factor. However, how this protein is secreted and the function of NELL2 in the brain has not been investigated. We now show that NELL2 localizes to the trans-golgi network and secreted to plasma membrane via both directional and non-directional mobility. The directional mobility of NELL2 vesicles is dependent mainly on microtubules, although actin filaments also participate in this process. Furthermore, NELL2 is selectively expressed in the two major subtypes of glutamatergic neurons described in the postnatal brain: those containing the vesicular glutamate transporter 1 and those expressing vesicular glutamate transporter 2. No NELL2 mRNA is detected in GABAergic neurons. Likewise, GnRH neurons are devoid of NELL2. NELL2 over-expression enhanced Ca2+-dependent glutamate release; its three Ca2+-binding EGF-like repeat domains play an important role in this process. One of the physiological processes controlled by glutamatergic neurons of the neuroendocrine brain is sexual development. During prepubertal development of the female rat, NELL2 mRNA is dramatically increased in the medial basal hypothalamus. In vivo disruption of NELL2 synthesis via intraventricular administration of antisense oligodeoxynucleotides reduced GnRH release from the medial basal hypothalamus and delayed the initiation of female puberty. These results identify NELL2 as a new component of glutamatergic neurons and provide evidence for its physiological involvement in a major, glutamate-dependent, process of neuroendocrine regulation.
