A PKM generated by calpain cleavage of a classical PKC is required for activity-dependent intermediate-term facilitation in the presynaptic sensory neuron of Aplysia.
A PKM generated by calpain cleavage of a classical PKC is required for activity-dependent intermediate-term facilitation in the presynaptic sensory neuron of Aplysia.
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DOI：
10.1101/lm.043745.116
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Sossin WS
中科院分区：
文献类型：
--
作者：
Farah CA;Hastings MH;Dunn TW;Gong K;Baker-Andresen D;Sossin WS
非典型PKM是非典型PKC的一种持续活性形式，被认为是一种分子记忆痕迹，但很少有人研究由其他PKC产生的PKM的作用。我们证明了用于抑制由非典型PKC产生的PKM的抑制剂也是其他PKM的有效抑制剂。相比之下，我们证明显性负性PKM显示亚型特异性。当在感觉神经元中表达时，来自经典PKC Apl I的显性负性PKM阻断活性依赖性中期易化（a-ITF），而来自非典型PKC Apl III的显性负性PKM不阻断。与PKM Apl I在活性依赖性易化中的特定作用一致，基于FRET的活体成像裂解试验揭示，在感觉神经元静脉曲张中，活性导致经典PKC Apl I裂解，但不导致非典型PKC Apl III裂解。与此相反，大量的中间易化（m-ITF）诱导的10分钟的5 HT是足够的分裂的非典型PKC Apl III的运动神经元。有趣的是，在a-ITF期间感觉神经元中PKC Apl I的裂解和在m-ITF期间运动神经元中PKC Apl III的裂解都被含有从Aaplasia克隆的经典钙蛋白酶的penta-EF手的显性负性形式抑制。与PKM在可塑性中的作用一致，这种显性负性钙蛋白酶也阻断在感觉神经元中表达的a-ITF和在运动神经元中表达的m-ITF。这项研究拓宽了PKM在突触可塑性中的作用，在两个重要的方式：（i）PKM产生的多种异构体的PKC，包括经典的异构体，保持记忆痕迹;（ii）PKM在突触前神经元中发挥作用。
Atypical PKM, a persistently active form of atypical PKC, is proposed to be a molecular memory trace, but there have been few examinations of the role of PKMs generated from other PKCs. We demonstrate that inhibitors used to inhibit PKMs generated from atypical PKCs are also effective inhibitors of other PKMs. In contrast, we demonstrate that dominant-negative PKMs show isoform-specificity. A dominant-negative PKM from the classical PKC Apl I blocks activity-dependent intermediate-term facilitation (a-ITF) when expressed in the sensory neuron, while a dominant-negative PKM from the atypical PKC Apl III does not. Consistent with a specific role for PKM Apl I in activity-dependent facilitation, live imaging FRET-based cleavage assays reveal that activity leads to cleavage of the classical PKC Apl I, but not the atypical PKC Apl III in the sensory neuron varicosities of Aplysia. In contrast, massed intermediate facilitation (m-ITF) induced by 10 min of 5HT is sufficient for cleavage of the atypical PKC Apl III in the motor neuron. Interestingly, both cleavage of PKC Apl I in the sensory neuron during a-ITF and cleavage of PKC Apl III in the motor neuron during m-ITF are inhibited by a dominant-negative form of a penta-EF hand containing classical calpain cloned from Aplysia. Consistent with a role for PKMs in plasticity, this dominant-negative calpain also blocks both a-ITF when expressed in the sensory neuron and m-ITF when expressed in the motor neuron. This study broadens the role of PKMs in synaptic plasticity in two significant ways: (i) PKMs generated from multiple isoforms of PKC, including classical isoforms, maintain memory traces; (ii) PKMs play roles in the presynaptic neuron.
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影响因子：
3.6
作者：
Sacktor TC
通讯作者：
Sacktor TC
DOI：
10.1523/jneurosci.0546-10.2010
发表时间：
2010-06-23
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Hu JY;Chen Y;Bougie JK;Sossin WS;Schacher S
通讯作者：
Schacher S
影响因子：
--
作者：
Antal, Corina E.;Violin, Jonathan D.;Newton, Alexandra C.
通讯作者：
Newton, Alexandra C.
影响因子：
5.3
作者：
Hu, Jiangyuan;Schacher, Samuel
通讯作者：
Schacher, Samuel
影响因子：
4.8
作者：
Hernandez, AI;Blace, N;Sacktor, TC
通讯作者：
Sacktor, TC