期刊
NEURON GLIA BIOLOGY
卷 1, 期 -, 页码 193-199出版社
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S1740925X05000013
关键词
ADNP; homeobox; brain development; microtubules; secreted proteins
资金
- US-Israel Bi-National Science Foundation
- Neufeld Award
- National Institutes of Health
- Sackler Faculty of Medicine/Tel-Aviv University in Women's Health
- Israel Science Foundation
- Institute for the Study of Aging
- Allon Therapeutics Inc
- FOGARTY INTERNATIONAL CENTER [F15TW000370] Funding Source: NIH RePORTER
Activity-dependent neuroprotective protein (ADNP, similar to 123562.8 Da), is synthesized in astrocytes and expression of A DNP mRNA is regulated by the neuroprotective peptide vasoactive intestinal peptide (VIP). The gene that encodes ADNP is conserved in human, rat and mouse, and contains a homeobox domain profile that includes a nuclear-export signal and a nuclear-localization signal. ADNP is essential for embryonic brain development, and NAP, an eight-amino acid peptide that is derived from ADNP, confers potent neuroprotection. Here, we investigate the subcellular localization of ADNP through cell fractionation, gel electrophoresis, immunoblotting and immunocytochemistry using alpha-CNAP, an antibody directed to the neuroprotective NAP fragment that constitutes part of an N-terminal epitope of ADNP. Recombinant ADNP was used as a competitive ligand to measure antibody specificity. ADNP-like immunoreactivity was found in the nuclear cell fraction of astrocytes and in the cytoplasm. In the cytoplasm, ADNP-like immunoreactivity colocalized with tubulin-like immunoreactivity and with microtubular structures, but not with actin microfilaments. Because microtubules are key components of developing neurons and brain, possible interaction between tubulin and ADNP might indicate a functional correlate to the role of ADNP in the brain. In addition, ADNP-like immunoreactivity in the extracellular milieu of astrocytes increased by similar to 1.4 fold after incubation of the astrocytes with VIP. VIP is known to cause astrocytes to secrete neuroprotective/neurotrophic factors, and we suggest that ADNP constitutes part of this VIP-stimulated protective milieu.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据