Involvement of advillin in somatosensory neuron subtype-specific axon regeneration and neuropathic pain.
Involvement of advillin in somatosensory neuron subtype-specific axon regeneration and neuropathic pain.
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DOI：
10.1073/pnas.1716470115
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发表时间：
2018-09-04
影响因子：
11.1
通讯作者：
Chen CC
中科院分区：
文献类型：
--
作者：
Chuang YC;Lee CH;Sun WH;Chen CC
据估计，在美国有2000万人患有慢性神经性疼痛，但目前的镇痛药是非特异性的或不够有效。在这里，我们表明，advillin，一种感觉神经元特异性蛋白，调节轴突再生的一个特定的子集的疼痛感觉传入神经元（伤害感受器），绑定与isolectin B4和神经性疼痛。此外，我们确定了细胞行为的adverlin脱落的轴突再生的背景下，从生长锥，从而检测到adverlin蛋白在小鼠的脑脊液中的疼痛性周围神经病变。Advillin是诊断与isolectin B4+伤害感受器相关的神经病理性疼痛的损伤原因的潜在生物标志物。Advillin是一种感觉神经元特异性肌动蛋白结合蛋白，在早期发育的所有类型的体感神经元中高水平表达。然而，adverillin在成年期的确切作用在很大程度上是未知的。在这里，我们揭示了advillin表达仅限于isolectin B4阳性（IB4+）的神经元在成人背根神经节（DRG）。Advillin敲除（KO）特异性损害成年IB4+ DRG神经元的轴突再生。在轴突再生过程中，advillin在丝状伪足的尖端表达，并通过与和调节局部粘附相关蛋白的相互作用来调节生长锥的形成。在轴突回缩过程中，含advillin的局灶性粘附蛋白复合物从轴突尖端脱落，并在实验性自身免疫性脑脊髓炎、奥沙利铂诱导的周围神经病和坐骨神经慢性压迫性损伤的脑脊液中检测到。此外，advillin KO干扰实验性自身免疫性脑脊髓炎诱导的脊髓背角神经可塑性，加重神经病理性疼痛。我们的研究强调了advillin在生长锥形成，轴突再生和与成年期IB4+ DRG神经元相关的神经性疼痛中的作用。
An estimated 20 million people in the United States have chronic neuropathic pain, but current analgesics are nonspecific or insufficiently effective. Here we show that advillin, a sensory neuron-specific protein, modulates axonal regeneration of a specific subset of pain-sensing afferent neurons (nociceptors) that binds with isolectin B4 and neuropathic pain. In addition, we identify the cell behavior of advillin shed-off from the growth cone in the context of axonal regeneration and thus detected advillin protein in the cerebrospinal fluid in mice with painful peripheral neuropathy. Advillin is a potential biosignature to diagnose the lesion cause of neuropathic pain associated with isolectin B4+ nociceptors. Advillin is a sensory neuron-specific actin-binding protein expressed at high levels in all types of somatosensory neurons in early development. However, the precise role of advillin in adulthood is largely unknown. Here we reveal advillin expression restricted to isolectin B4-positive (IB4+) neurons in the adult dorsal root ganglia (DRG). Advillin knockout (KO) specifically impaired axonal regeneration in adult IB4+ DRG neurons. During axon regeneration, advillin was expressed at the very tips of filopodia and modulated growth cone formation by interacting with and regulating focal-adhesion–related proteins. The advillin-containing focal-adhesion protein complex was shed from neurite tips during neurite retraction and was detectable in cerebrospinal fluid in experimental autoimmune encephalomyelitis, oxaliplatin-induced peripheral neuropathy, and chronic constriction injury of the sciatic nerve. In addition, advillin KO disturbed experimental autoimmune encephalomyelitis-induced neural plasticity in the spinal-cord dorsal horn and aggravated neuropathic pain. Our study highlights a role for advillin in growth cone formation, axon regeneration, and neuropathic pain associated with IB4+ DRG neurons in adulthood.
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DOI：
10.1073/pnas.1003287107
发表时间：
2010-06-22
影响因子：
11.1
作者：
Harvey, Pamela;Gong, BangJian;Frank, Eric
通讯作者：
Frank, Eric
影响因子：
5.3
作者：
Casals-Diaz, Laura;Vivo, Meritxell;Navarro, Xavier
通讯作者：
Navarro, Xavier
影响因子：
3
作者：
Gardiner, Natalie J.
通讯作者：
Gardiner, Natalie J.
影响因子：
13.9
作者：
Costigan M;Scholz J;Woolf CJ
通讯作者：
Woolf CJ
影响因子：
21.3
作者：
Ezratty, EJ;Partridge, MA;Gundersen, GG
通讯作者：
Gundersen, GG