Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, 112 Taipei, Taiwan.
Institute of Biomedical Sciences, Academia Sinica, 115 Taipei, Taiwan.
Proc Natl Acad Sci U S A. 2018 Sep 4;115(36):E8557-E8566. doi: 10.1073/pnas.1716470115. Epub 2018 Aug 20.
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.
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感觉神经元中高水平表达。然而，advillin 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 表达局限于成年背根神经节（DRG）中异硫氰酸荧光素结合蛋白 4 阳性（IB4）神经元。advillin 敲除（KO）特异性损害了成年 IB4 DRG 神经元的轴突再生。在轴突再生过程中，advillin 表达在丝状伪足的尖端，并通过与和调节焦点附着相关蛋白相互作用来调节生长锥的形成。含有 advillin 的焦点附着蛋白复合物在神经突回缩过程中从神经突尖端脱落，并可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缩窄性损伤的脑脊液中检测到。此外，advillin KO 干扰了实验性自身免疫性脑脊髓炎诱导的脊髓背角中的神经可塑性，并加重了神经病理性疼痛。我们的研究强调了 advillin 在成年 IB4 DRG 神经元的生长锥形成、轴突再生和神经病理性疼痛中的作用。
