Compositional complexity of rods and rings

Molecular Biology of the Cell
Cara R SchiavonRichard A Kahn

Abstract

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.

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Citations

May 14, 2019·Viral Immunology·Tarak DhaouadiYousr Gorgi
May 29, 2020·Molecular Biology of the Cell·Jacqueline C SimonetJeffrey R Peterson
May 16, 2019·Molecular Biology of the Cell·Elizabeth SztulRichard A Kahn
Aug 18, 2020·Autoimmunity Reviews·S John Calise, Edward K L Chan
Aug 20, 2020·Chemical Reviews·Hongjian HeBing Xu
Feb 18, 2021·Molecular Biology of the Cell·Rachel E TurnRichard A Kahn
Aug 22, 2021·Autoimmunity Reviews·Shingo KatayamaHiroki Shiwaku
Sep 10, 2021·Journal of Neuropathology and Experimental Neurology·Narges AhangariJohn Woulfe

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Datasets Mentioned

BETA
AB120335

Methods Mentioned

BETA
GTPase
electron microscopy
GTPases
transmission electron microscopy
transfection

Software Mentioned

ImageJ
AICAR
Fluoview
Olympus

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