scholarly journals ESCRT-II controls retinal axon growth by regulating DCC receptor levels and local protein synthesis

Open Biology ◽  
2016 ◽  
Vol 6 (4) ◽  
pp. 150218 ◽  
Author(s):  
Filip A. Konopacki ◽  
Hovy Ho-Wai Wong ◽  
Asha Dwivedy ◽  
Anaïs Bellon ◽  
Michael D. Blower ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Axon Growth ◽  
Endocytic Pathway ◽  
Loss Of Function ◽  
Gradient Sensing ◽  
Deleted In Colorectal Cancer ◽  
Local Protein Synthesis ◽  
Local Protein

Endocytosis and local protein synthesis (LPS) act coordinately to mediate the chemotropic responses of axons, but the link between these two processes is poorly understood. The endosomal sorting complex required for transport (ESCRT) is a key regulator of cargo sorting in the endocytic pathway, and here we have investigated the role of ESCRT-II, a critical ESCRT component, in Xenopus retinal ganglion cell (RGC) axons. We show that ESCRT-II is present in RGC axonal growth cones (GCs) where it co-localizes with endocytic vesicle GTPases and, unexpectedly, with the Netrin-1 receptor, deleted in colorectal cancer (DCC). ESCRT-II knockdown (KD) decreases endocytosis and, strikingly, reduces DCC in GCs and leads to axon growth and guidance defects. ESCRT-II-depleted axons fail to turn in response to a Netrin-1 gradient in vitro and many axons fail to exit the eye in vivo . These defects, similar to Netrin-1/DCC loss-of-function phenotypes, can be rescued in whole ( in vitro ) or in part ( in vivo ) by expressing DCC. In addition, ESCRT-II KD impairs LPS in GCs and live imaging reveals that ESCRT-II transports mRNAs in axons. Collectively, our results show that the ESCRT-II-mediated endocytic pathway regulates both DCC and LPS in the axonal compartment and suggest that ESCRT-II aids gradient sensing in GCs by coupling endocytosis to LPS.

scholarly journals Presynaptic FMRP and local protein synthesis support structural and functional plasticity of glutamatergic axon terminals

2021 ◽  
Author(s):  
Hannah R Monday ◽  
Shivani C Kharod ◽  
Young J Yoon ◽  
Robert H Singer ◽  
Pablo E Castillo
Keyword(s):  
Protein Synthesis ◽  
Rna Binding ◽  
Mossy Fiber ◽  
Fragile X ◽  
Long Term Potentiation ◽  
Local Protein Synthesis ◽  
Axon Terminals ◽  
Local Protein

Learning and memory critically rely on long-lasting, synapse-specific modifications. While postsynaptic forms of plasticity typically require local protein synthesis, whether and how local protein synthesis contributes to presynaptic changes remains unclear. Here, we examined the hippocampal mossy fiber (MF)-CA3 synapse which expresses both structural and functional presynaptic plasticity. We report that MF boutons synthesize protein locally and contain ribosomes. Long-term potentiation of MF-CA3 synaptic transmission (MF-LTP) was associated with translation-dependent enlargement of MF boutons. Moreover, increasing in vitro and in vivo MF activity enhanced protein synthesis in MFs. Remarkably, deletion of presynaptic Fragile X mental retardation protein (FMRP), an RNA-binding protein expressed in MF boutons and previously implicated in local postsynaptic protein synthesis-dependent plasticity, blocked structural and functional MF-LTP, suggesting that FMRP is a critical regulator of presynaptic function. Thus, presynaptic FMRP and protein synthesis dynamically control presynaptic structure and function in the mature brain.

Early regeneration in vitro of adult mouse sciatic axons is dependent on local protein synthesis but may not involve neurotrophins

1994 ◽  
Vol 168 (1-2) ◽  
pp. 37-40 ◽  
Author(s):  
Magnus Edbladh ◽  
David Tonge ◽  
Jon Golding ◽  
Per A.R. Ekström ◽  
Anders Edström
Keyword(s):  
Protein Synthesis ◽  
Adult Mouse ◽  
Local Protein Synthesis ◽  
Regeneration In Vitro ◽  
Early Regeneration ◽  
Local Protein

scholarly journals DSCR1 is required for both axonal growth cone extension and steering

2016 ◽  
Vol 213 (4) ◽  
pp. 451-462 ◽  
Author(s):  
Wei Wang ◽  
Asit Rai ◽  
Eun-Mi Hur ◽  
Zeev Smilansky ◽  
Karen T. Chang ◽  
...  
Keyword(s):  
Nervous System ◽  
Protein Synthesis ◽  
Growth Cone ◽  
Actin Polymerization ◽  
Axon Growth ◽  
Axon Outgrowth ◽  
Actin Dynamics ◽  
Local Protein Synthesis ◽  
Axon Extension ◽  
Local Protein

Local information processing in the growth cone is essential for correct wiring of the nervous system. As an axon navigates through the developing nervous system, the growth cone responds to extrinsic guidance cues by coordinating axon outgrowth with growth cone steering. It has become increasingly clear that axon extension requires proper actin polymerization dynamics, whereas growth cone steering involves local protein synthesis. However, molecular components integrating these two processes have not been identified. Here, we show that Down syndrome critical region 1 protein (DSCR1) controls axon outgrowth by modulating growth cone actin dynamics through regulation of cofilin activity (phospho/dephospho-cofilin). Additionally, DSCR1 mediates brain-derived neurotrophic factor–induced local protein synthesis and growth cone turning. Our study identifies DSCR1 as a key protein that couples axon growth and pathfinding by dually regulating actin dynamics and local protein synthesis.

scholarly journals Single Molecule Translation Imaging of Local Protein Synthesis and RNA Docking Reveals the Regulation of Site Specific Axon Remodeling In Vivo

2018 ◽  
Vol 114 (3) ◽  
pp. 153a
Author(s):  
Clemens F. Kaminski ◽  
Hovy Ho-Wai Wong ◽  
Florian Strohl ◽  
Julie Quiaojin Lin ◽  
Christine E. Holt
Keyword(s):  
Protein Synthesis ◽  
Single Molecule ◽  
Site Specific ◽  
Local Protein Synthesis ◽  
Local Protein

scholarly journals The piRNA pathway sustains adult neurogenesis by repressing protein synthesis

2020 ◽  
Author(s):  
C. Gasperini ◽  
R. Pelizzoli ◽  
A. Lo Van ◽  
D. Mangoni ◽  
R.M. Cossu ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Adult Neurogenesis ◽  
Neural Progenitor Cells ◽  
Brain Plasticity ◽  
Mammalian Brain ◽  
Loss Of Function ◽  
Transfer Rnas ◽  
Pirna Pathway

AbstractIn specific niches of the adult mammalian brain, neural progenitor cells (aNPCs) ensure lifelong neurogenesis. Proper regulation of this process entails important implications for brain plasticity and health. We report that Piwil2 (Mili) and PIWI-interacting RNAs (piRNAs) are abundantly expressed in aNPCs but depleted in their progeny in the adult mouse hippocampus. Loss of function of the piRNA pathway in aNPCs inhibited neurogenesis and increased reactive gliogenesis in vivo and in vitro. PiRNA pathway depletion in cultured aNPCs increased levels of 5S ribosomal RNA, transfer RNAs and mRNAs encoding regulators of translation, resulting in higher polyribosome density and protein synthesis upon differentiation. We propose that the piRNA pathway sustains adult neurogenesis by repressing translation in aNPCs.One sentence summaryThe piRNA pathway is enriched in neural precursors and essential for appropriate neurogenesis by modulating translation

Dendritic ribosomes suggest local protein synthesis during estrous synaptogenesis

Neuroreport ◽  
2003 ◽  
Vol 14 (10) ◽  
pp. 1357-1360 ◽  
Author(s):  
J. Brian McCarthy ◽  
Teresa A. Milner
Keyword(s):  
Protein Synthesis ◽  
Local Protein Synthesis ◽  
Local Protein

scholarly journals TRIM27 interacts with Iκbα to promote the growth of human renal cancer cells through regulating the NF-κB pathway

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chengwu Xiao ◽  
Wei Zhang ◽  
Meimian Hua ◽  
Huan Chen ◽  
Bin Yang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Abstract Background The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC. Methods The mRNA levels of TRIM27 and Kaplan–Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression. Results We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation. Conclusions Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.

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