Inhibition of Axon Regeneration by Liquid-like TIAR-2 Granules

Autor: Panid Sharifnia, Matthew G. Andrusiak, Yishi Jin, Xiaohui Lyu, Zilu Wu, Andrea M. Dickey, Andrew D. Chisholm, Zhiping Wang
Rok vydání: 2018
Předmět:
0301 basic medicine
RNA granule
TIA1
RNA-binding protein
1.1 Normal biological development and functioning
Neurodegenerative
stress granule
Regenerative Medicine
Cytoplasmic Granules
Serine
03 medical and health sciences
prion-like domain
0302 clinical medicine
Stress granule
Protein Domains
Underpinning research
medicine
Psychology
Animals
Tyrosine
Axon
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Neurology & Neurosurgery
Chemistry
General Neuroscience
Granule (cell biology)
axon regeneration
Neurosciences
RNA-Binding Proteins
liquid-liquid phase separation
tiar-2
C. elegans
Axons
Cell biology
Cell Compartmentation
Nerve Regeneration
T-Cell Intracellular Antigen-1
030104 developmental biology
medicine.anatomical_structure
RNA Recognition Motif Proteins
axon injury
Phosphorylation
LLPS
Cognitive Sciences
030217 neurology & neurosurgery
Zdroj: Neuron, vol 104, iss 2
ISSN: 1097-4199
Popis: Phase separation into liquid-like compartments is an emerging property of proteins containing prion-like domains (PrLDs), yet the invivo roles of phase separation remain poorly understood. TIA proteins contain a C-terminal PrLD, and mutations in the PrLD are associated with several diseases. Here, we show that the C.elegans TIAR-2/TIA protein functions cell autonomously to inhibit axon regeneration. TIAR-2 undergoes liquid-liquid phase separation invitro and forms granules with liquid-like properties invivo. Axon injury induces a transient increase in TIAR-2 granule number. The PrLD is necessary and sufficient for granule formation and inhibiting regeneration. Tyrosine residues within the PrLD are important for granule formation and inhibition of regeneration. TIAR-2 is also serine phosphorylated invivo. Non-phosphorylatable TIAR-2 variants do not form granules and are unable to inhibit axon regeneration. Our data demonstrate an invivo function for phase-separated TIAR-2 and identify features critical for its function in axon regeneration.
Databáze: OpenAIRE
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