scholarly journals Prenylation of axonally translated proteins controls NGF-dependent axon growth

2020 ◽  
Author(s):  
Emily Scott-Solomon ◽  
Rejji Kuruvilla
Keyword(s):  
Protein Synthesis ◽  
Neuronal Development ◽  
Axon Growth ◽  
Axonal Growth ◽  
Cellular Functions ◽  
Protein Prenylation ◽  
Local Protein Synthesis ◽  
Extrinsic Cues ◽  
Rac1 Gtpase ◽  
Axonal Protein

SummaryCompartmentalized signaling is critical for cellular organization and specificity of functional outcomes in neurons. Here, we report that post-translational lipidation of newly synthesized proteins in axonal compartments allows for short-term and autonomous responses to extrinsic cues. Using conditional mutant mice, we found that protein prenylation is essential for sympathetic axon innervation of target organs. We identify a localized requirement for prenylation in sympathetic axons to promote axonal growth in response to the neurotrophin, Nerve Growth Factor (NGF). NGF triggers prenylation of proteins including the Rac1 GTPase in axons, counter to the canonical view of prenylation as constitutive, and strikingly, in a manner dependent on axonal protein synthesis. Newly prenylated proteins localize to TrkA-harboring endosomes in axons, and promote receptor trafficking necessary for axonal growth. Thus, coupling of prenylation to local protein synthesis presents a mechanism for spatially segregated cellular functions during neuronal development.

scholarly journals Differential requirement of F-actin and microtubule cytoskeleton in cue-induced local protein synthesis in axonal growth cones

2015 ◽  
Vol 10 (1) ◽  
pp. 3 ◽  
Author(s):  
Michael Piper ◽  
Aih Lee ◽  
Francisca van Horck ◽  
Heather McNeilly ◽  
Trina Lu ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Axonal Growth ◽  
Growth Cones ◽  
Microtubule Cytoskeleton ◽  
Local Protein Synthesis ◽  
Local Protein

scholarly journals Local protein synthesis of neuronal MT1-MMP for agrin-induced presynaptic development

Development ◽  
2021 ◽  
Vol 148 (10) ◽  
Author(s):  
Jun Yu ◽  
Marilyn Janice Oentaryo ◽  
Chi Wai Lee
Keyword(s):  
Protein Synthesis ◽  
Neuronal Development ◽  
Neuromuscular Junctions ◽  
Neuronal Cell ◽  
Time Lapse ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Local Protein Synthesis ◽  
Presynaptic Differentiation ◽  
Local Protein

ABSTRACT Upon the stimulation of extracellular cues, a significant number of proteins are synthesized distally along the axon. Although local protein synthesis is crucial for various stages throughout neuronal development, its involvement in presynaptic differentiation at developing neuromuscular junctions remains unknown. By using axon severing and microfluidic chamber assays, we first showed that treatment of a protein synthesis inhibitor, cycloheximide, inhibits agrin-induced presynaptic differentiation in cultured Xenopus spinal neurons. Newly synthesized proteins are prominently detected, as revealed by the staining of click-reactive cell-permeable puromycin analog O-propargyl-puromycin, at agrin bead-neurite contacts involving the mTOR/4E-BP1 pathway. Next, live-cell time-lapse imaging demonstrated the local capturing and immobilization of ribonucleoprotein granules upon agrin bead stimulation. Given that our recent study reported the roles of membrane-type 1 matrix metalloproteinase (MT1-MMP) in agrin-induced presynaptic differentiation, here we further showed that MT1-MMP mRNA is spatially enriched and locally translated at sites induced by agrin beads. Taken together, this study reveals an essential role for axonal MT1-MMP translation, on top of the well-recognized long-range transport of MT1-MMP proteins synthesized from neuronal cell bodies, in mediating agrin-induced presynaptic differentiation.

scholarly journals Erratum to: Differential requirement of F-actin and microtubule cytoskeleton in cue-induced local protein synthesis in axonal growth cones

2015 ◽  
Vol 10 (1) ◽  
Author(s):  
Michael Piper ◽  
Aih Cheun Lee ◽  
Francisca P.G van Horck ◽  
Heather McNeilly ◽  
Trina Bo Lu ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Axonal Growth ◽  
Growth Cones ◽  
Microtubule Cytoskeleton ◽  
Local Protein Synthesis ◽  
Local Protein

scholarly journals Local Protein Synthesis in Axonal Growth Cones

2007 ◽  
Vol 1 (4) ◽  
pp. 179-184 ◽  
Author(s):  
Saulius Satkauskas ◽  
Dominique Bagnard
Keyword(s):  
Protein Synthesis ◽  
Axonal Growth ◽  
Growth Cones ◽  
Local Protein Synthesis ◽  
Local Protein

scholarly journals Distinct roles for sphingolipids and glycosphingolipids at different stages of neuronal development.

1998 ◽  
Vol 45 (2) ◽  
pp. 469-478 ◽  
Author(s):  
A H Futerman
Keyword(s):  
Intracellular Transport ◽  
Neuronal Development ◽  
Apoptotic Cell ◽  
Primary Cultures ◽  
Axon Growth ◽  
Axonal Growth ◽  
Neuronal Cultures ◽  
Subsequent Stage ◽  
Transport Pathway ◽  
Sequence Of Events

Studies on the roles of sphingolipids (SLs) and glycosphingolipids (GSLs) at distinct stages of neuronal development have been performed using primary cultures of hippocampal neurons, which are unique among neuronal cultures inasmuch as they develop by a well-characterized and stereotypic sequence of events that gives rise to fully differentiated axons and dendrites. Our data demonstrate that SLs and GSLs play at least three distinct roles in regulating neuronal development, namely: (i) ceramide enhances the formation of minor neuronal processes from lamellipodia and the subsequent stage of axonogenesis; (ii) glucosylceramide synthesis, but not the synthesis of higher-order GSLs, is required for normal axon growth and for accelerated axonal growth upon stimulation by growth factors; and (iii) at both of these stages, ceramide at high concentrations can induce apoptotic cell death. Together, these observations are consistent with the possibility that minor process formation and apoptosis are regulated by ceramide-dependent signaling pathways, whereas axonal growth requires glucosylceramide synthesis, perhaps to support an intracellular transport pathway.

scholarly journals Regulation of retinal axon growth by secreted Vax1 homeodomain protein

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Namsuk Kim ◽  
Kwang Wook Min ◽  
Kyung Hwa Kang ◽  
Eun Jung Lee ◽  
Hyoung-Tai Kim ◽  
...  
Keyword(s):  
Axon Growth ◽  
Axonal Growth ◽  
Optic Chiasm ◽  
Homeodomain Protein ◽  
Retinal Ganglion ◽  
Factor Activity ◽  
Local Protein Synthesis ◽  
Hypothalamic Cells ◽  
Retinal Axon ◽  
Local Protein

Retinal ganglion cell (RGC) axons of binocular animals cross the midline at the optic chiasm (OC) to grow toward their synaptic targets in the contralateral brain. Ventral anterior homeobox 1 (Vax1) plays an essential role in the development of the OC by regulating RGC axon growth in a non-cell autonomous manner. In this study, we identify an unexpected function of Vax1 that is secreted from ventral hypothalamic cells and diffuses to RGC axons, where it promotes axonal growth independent of its transcription factor activity. We demonstrate that Vax1 binds to extracellular sugar groups of the heparan sulfate proteoglycans (HSPGs) located in RGC axons. Both Vax1 binding to HSPGs and subsequent penetration into the axoplasm, where Vax1 activates local protein synthesis, are required for RGC axonal growth. Together, our findings demonstrate that Vax1 possesses a novel RGC axon growth factor activity that is critical for the development of the mammalian binocular visual system.

FMRP and MicroRNAs in Neuronal Protein Synthesis

2018 ◽  
Author(s):  
Monica C. Lannom ◽  
Stephanie Ceman
Keyword(s):  
Protein Synthesis ◽  
Binding Proteins ◽  
Neuronal Development ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Post Translational Modifications ◽  
Local Protein Synthesis ◽  
Recognition Element ◽  
Neuronal Protein ◽  
And Function

New protein synthesis is critical for learning and memory. The discovery of ribosomes at synapses indicated the potential for local protein synthesis in response to stimulation. miRNAs play a key role in this process as evidenced by their role in normal neuronal development and function and in neurological disease. miRNA production is regulated and once bound by AGO2, the ensuing RISC complex is able to bind mRNAs and direct their translation suppression and degradation. However, other RNA binding proteins, including FMRP and MOV10, regulate AGO2 association with the miRNA recognition element (MRE) in target mRNAs. AGO2 itself is regulated by post-translational modifications, and neuronal activity controls post-translational modifications of FMRP and MOV10 that lead to their regulation and degradation. In addition, RNA localization at the synapse is a critical regulated event that depends on both cis sequences in the mRNA and the identity of the bound RNA binding proteins.

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 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.

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