Annexin A1 complex mediates oxytocin vesicle transport.
Annexin A1 complex mediates oxytocin vesicle transport.
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DOI：
10.1111/jne.12112
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发表时间：
2013-12
影响因子：
3.2
通讯作者：
Park J
中科院分区：
文献类型：
--
作者：
Makani V;Sultana R;Sie KS;Orjiako D;Tatangelo M;Dowling A;Cai J;Pierce W;Butterfield DA;Hill J;Park J
催产素是一种主要的神经肽，调节参与社会行为和互动的大脑功能。尽管催产素对社会行为的神经控制很重要，但对大脑中催产素分泌调节的分子机制知之甚少。催产素原在视上核和室旁核的下丘脑神经元的细胞体中合成，并在后高尔基体运输到轴突末端和体树突区域的分泌位点期间加工成9-氨基酸成熟形式。从体树突区域分泌的催产素扩散到整个下丘脑及其邻近的脑区域。一些催产素阳性轴突支配并分泌催产素到下丘脑远端的脑区。大脑催产素与其在参与社会行为的大脑区域的受体结合。催产素也从垂体后叶的轴突末端分泌到血液循环中。我们已经发现了一种新的分子复合物，由膜联蛋白A1（ANXA 1），A-激酶锚蛋白150（AKAP 150），和微管马达，控制催产素囊泡之间的分布轴突和细胞体的蛋白激酶A（PKA）和蛋白激酶C（PKC）敏感的方式。ANXA 1与催产素囊泡显示出显著的共定位。PKA的激活增强了驱动蛋白2与ANXA 1的结合，从而增加了催产素囊泡的轴突定位。相反，PKC的激活降低了驱动蛋白-2与ANXA 1的结合，从而减弱了催产素囊泡的轴突定位。我们的研究表明，ANXA 1复合物协调PKA和PKC的行动，以控制轴突和细胞体之间的催产素囊泡的分布。
Oxytocin is a major neuropeptide that modulates the brain functions involved in social behavior and interaction. Despite of the importance of oxytocin for neural control of social behavior, little is known about the molecular mechanism(s) by which oxytocin secretion in the brain is regulated. Pro-oxytocin is synthesized in the cell bodies of hypothalamic neurons in the supraoptic and paraventricular nuclei and processed to a 9-amino-acid mature form during post-Golgi transport to the secretion sites at the axon terminals and somatodendritic regions. Oxytocin secreted from the somatodendritic regions diffuses throughout the hypothalamus and its neighboring brain regions. Some oxytocin-positive axons innervate and secrete oxytocin to the brain regions distal to the hypothalamus. Brain oxytocin binds to its receptors in the brain regions involved in social behavior. Oxytocin is also secreted from the axon terminal at the posterior pituitary gland into the blood circulation. We have discovered a new molecular complex consisting of annexin A1 (ANXA1), A-kinase anchor protein 150 (AKAP150), and microtubule motor, that controls the distribution of oxytocin vesicles between the axon and the cell body in a protein kinase A (PKA)- and protein kinase C (PKC)-sensitive manner. ANXA1 showed significant co-localization with oxytocin vesicles. Activation of PKA enhanced the association of kinesin-2 with ANXA1, thus increasing the axon-localization of oxytocin vesicles. Conversely, activation of PKC decreased the binding of kinesin-2 to ANXA1, thus attenuating the axon-localization of oxytocin vesicles. Our study suggests that ANXA1 complex coordinates the actions of PKA and PKC to control the distribution of oxytocin vesicles between the axon and the cell body.
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DOI：
10.1523/jneurosci.5175-09.2010
发表时间：
2010-02-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bal M;Zhang J;Hernandez CC;Zaika O;Shapiro MS
通讯作者：
Shapiro MS
影响因子：
4.6
作者：
Carnegie, Graeme K.;Means, Christopher K.;Scott, John D.
通讯作者：
Scott, John D.
影响因子：
3.6
作者：
Buckingham, JC;Solito, E;Morris, J
通讯作者：
Morris, J
DOI：
10.1073/pnas.1215462109
发表时间：
2012-11-06
影响因子：
11.1
作者：
Hendricks, Adam G.;Holzbaur, Erika L. F.;Goldman, Yale E.
通讯作者：
Goldman, Yale E.
影响因子：
5.5
作者：
Hirasawa, M;Kombian, SB;Pittman, QJ
通讯作者：
Pittman, QJ