Compositional complexity of rods and rings.
Compositional complexity of rods and rings.
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DOI：
10.1091/mbc.e18-05-0274
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发表时间：
2018-09-15
影响因子：
3.3
通讯作者：
Kahn RA
中科院分区：
文献类型：
--
作者：
Schiavon CR;Griffin ME;Pirozzi M;Parashuraman R;Zhou W;Jinnah HA;Reines D;Kahn RA
棒状和环状（rr）是大的线性或圆形结构，通常被描述为IMPDH（肌苷单磷酸脱氢酶）的聚合物。它们已经在多种细胞类型和物种中被观察到，并且可以通过IMPDH抑制剂诱导形成。RRs被认为在从头鸟嘌呤核苷酸合成的调控中发挥作用；然而，人们对rr的功能和调控知之甚少。在这里，我们发现调节性GTPase， ARL2，其结合伙伴的一个子集，以及内质网（ER）上的几个常驻蛋白也定位于rs。我们还发现了两种新的RR形成诱导剂：AICAR和葡萄糖剥夺。我们证明，如果鸟嘌呤核苷酸可以通过回收合成产生，不管诱导物是什么，RRs都可以被分解。最后，我们发现，随着rr的成熟，有一个有序的组分添加，IMPDH首先形成聚集体，其次是ARL2，然后是钙连蛋白（ER的标记物）。这些发现表明，RRs比以前认为的要复杂得多，RRs的功能可能包括参与一种调节性GTPase及其效应物，并可能与细胞膜接触。
Rods and rings (RRs) are large linear- or circular-shaped structures typically described as polymers of IMPDH (inosine monophosphate dehydrogenase). They have been observed across a wide variety of cell types and species and can be induced to form by inhibitors of IMPDH. RRs are thought to play a role in the regulation of de novo guanine nucleotide synthesis; however, the function and regulation of RRs is poorly understood. Here we show that the regulatory GTPase, ARL2, a subset of its binding partners, and several resident proteins at the endoplasmic reticulum (ER) also localize to RRs. We also have identified two new inducers of RR formation: AICAR and glucose deprivation. We demonstrate that RRs can be disassembled if guanine nucleotides can be generated by salvage synthesis regardless of the inducer. Finally, we show that there is an ordered addition of components as RRs mature, with IMPDH first forming aggregates, followed by ARL2, and only later calnexin, a marker of the ER. These findings suggest that RRs are considerably more complex than previously thought and that the function(s) of RRs may include involvement of a regulatory GTPase, its effectors, and potentially contacts with intracellular membranes.