The Novel GTPase Rit Differentially Regulates Axonal and Dendritic Growth

Lein, Pamela J.; Guo, Xin; Shi, Guangpu; Moholt-Siebert, Melissa; Bruun, Donald A.; Andres, Douglas A.

doi:10.1523/jneurosci.5633-06.2007

Cited by 53 publications

(102 citation statements)

References 69 publications

(102 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gyrus-RIT1 loss sensitizes immature hippocampal neurons to stress-dependent apoptosis and blunts hippocampal neural progenitor cell activation following traumatic brain injury (23). Consistent with a role for RIT1 in regulating adult neurogenesis, semiquantitative RT-PCR analysis confirmed RIT1 expression in both neurogenic niches of the CNS (Fig.…”

Section: Rit1 Is Expressed In the Dentatesupporting

confidence: 62%

“…RIT1 is widely expressed, including throughout the human and mouse brain (22)(23)(24). At the molecular level, we have previously described roles for RIT1 in the regulation of axonal and dendritic growth (23), activation of Akt (25)(26)(27), and control of cAMP response element-binding protein transcriptional activity (27). More recently, we identified a role for RIT1 in the survival of adultborn hippocampal neurons following traumatic brain injury (28).…”

mentioning

confidence: 99%

“…Functioning with their allied regulatory and effector protein networks, Ras-related GTPases serve as critical cellular biotimers, coupling diverse cellular stimuli to the spatial and temporal regulation of signal transduction pathways that contribute to almost every aspect of cellular physiology. RIT1 is widely expressed, including throughout the human and mouse brain (22)(23)(24). At the molecular level, we have previously described roles for RIT1 in the regulation of axonal and dendritic growth (23), activation of Akt (25)(26)(27), and control of cAMP response element-binding protein transcriptional activity (27).…”

mentioning

confidence: 99%

See 2 more Smart Citations

RIT1 GTPase Regulates Sox2 Transcriptional Activity and Hippocampal Neurogenesis

Mir

Cai

Andres

2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by Paul E. FraserAdult neurogenesis, the process of generating mature neurons from neuronal progenitor cells, makes critical contributions to neural circuitry and brain function in both healthy and disease states. Neurogenesis is a highly regulated process in which diverse environmental and physiological stimuli are relayed to resident neural stem cell populations to control the transcription of genes involved in self-renewal and differentiation. Understanding the molecular mechanisms governing neurogenesis is necessary for the development of translational strategies to harness this process for neuronal repair. Here we report that the Ras-related GTPase RIT1 serves to control the sequential proliferation and differentiation of adult hippocampal neural progenitor cells, with in vivo expression of active RIT1 driving robust adult neurogenesis. Gene expression profiling analysis demonstrates increased expression of a specific set of transcription factors known to govern adult neurogenesis in response to active RIT1 expression in the hippocampus, including sex-determining region Y-related HMG box 2 (Sox2), a well established regulator of stem cell self-renewal and neurogenesis. In adult hippocampal neuronal precursor cells, RIT1 controls an Akt-dependent signaling cascade, resulting in the stabilization and transcriptional activation of phosphorylated Sox2. This study supports a role for RIT1 in relaying niche-derived signals to neural/stem progenitor cells to control transcription of genes involved in self-renewal and differentiation.

show abstract

Section: Rit1 Is Expressed In the Dentatesupporting

confidence: 62%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

RIT1 GTPase Regulates Sox2 Transcriptional Activity and Hippocampal Neurogenesis

Mir

Cai

Andres

2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…In axonal outgrowth and extension, an increasing amount of data suggests that membrane supply and targeting of proteins are regulated in a different way compared with dendritic elongation (Silverman et al, 2001; This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08 -09 -0957) on February 11, 2009. Horton et al, 2005;Lein et al, 2007;Takemoto-Kimura et al, 2007;Ye et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…© 2009 by The American Society for Cell Biology Horton et al, 2005;Lein et al, 2007;Takemoto-Kimura et al, 2007;Ye et al, 2007). Based on studies in nonneuronal cells, protein kinase D (PKD) is known to play a key regulatory role in secretory pathways.…”

mentioning

confidence: 99%

Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

Czöndör

Ellwanger²,

Fuchs³

et al. 2009

MBoC

View full text Add to dashboard Cite

Protein kinase D (PKD) is known to participate in various cellular functions, including secretory vesicle fission from theGolgi and plasma membrane-directed transport. Here, we report on expression and function of PKD in hippocampal neurons. Expression of an enhanced green fluorescent protein (EGFP)-tagged PKD activity reporter in mouse embryonal hippocampal neurons revealed high endogenous PKD activity at the Golgi complex and in the dendrites, whereas PKD activity was excluded from the axon in parallel with axonal maturation. Expression of fluorescently tagged wild-type PKD1 and constitutively active PKD1 S738/742E (caPKD1) in neurons revealed that both proteins were slightly enriched at the trans-Golgi network (TGN) and did not interfere with its thread-like morphology. By contrast, expression of dominant-negative kinase inactive PKD1 K612W (kdPKD1) led to the disruption of the neuronal Golgi complex, with kdPKD1 strongly localized to the TGN fragments. Similar findings were obtained from transgenic mice with inducible, neuron-specific expression of kdPKD1-EGFP. As a prominent consequence of kdPKD1 expression, the dendritic tree of transfected neurons was reduced, whereas caPKD1 increased dendritic arborization. Our results thus provide direct evidence that PKD activity is selectively involved in the maintenance of dendritic arborization and Golgi structure of hippocampal neurons. INTRODUCTIONNeurons are nondividing and extremely polarized cells, with enormous membrane surface compared with the size of the soma. These features assume a highly specialized secretory machinery, which resembles in certain parts the directed transport mechanisms described in polarized nonneuronal cells (Winckler and Mellman, 1999;Horton and Ehlers, 2004). The vast neuronal membrane surface is functionally and structurally divided into axonal and somatodendritic compartments, possessing specific lipid and protein components required for the spatially different functions, e.g., for pre-or postsynaptic activity (Dresbach et al., 2001;Sheng, 2001;Bresler et al., 2004). The constitutive and precisely directed supply of surface membrane components is indispensable for the function of neurons, especially when considering that postmitotic neurons normally serve throughout the life span of the organism. Up to now, we are far from understanding how the extreme polarization has been evolved and is maintained in neurons.Despite a likely central role in neuronal morphogenesis and membrane trafficking, little is known about the special structure and transport features of the neuronal Golgi apparatus. A thread-like and reticular structure of the Golgi apparatus has been already described in many neuronal types (Takamine et al., 2000;Fujita and Okamoto, 2005;Horton et al., 2005). Central neuronal Golgi complex is localized in the soma and often extends into the principal dendrites, but Golgi elements were also found as discontinuous structures in the distal dendrites, often near synaptic contacts or in dendritic spines (Gardiol et al., 1999;Pierc...

show abstract

Molecular and clinical delineation of 2p15p16.1 microdeletion syndrome

Lévy

Coussement

Dupont

et al. 2017

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Interstitial 2p15p16.1 microdeletion is a rare chromosomal syndrome previously reported in 33 patients. It is characterized by intellectual disability, developmental delay, autism spectrum disorders, microcephaly, short stature, dysmorphic features, and multiple congenital organ defects. It is defined as a contiguous gene syndrome and two critical regions have been proposed at 2p15 and 2p16.1 loci. Nevertheless, patients with deletion of both critical regions shared similar features of the phenotype and the correlation genotype-phenotype is still unclear. We review all published cases and describe three additional patients, to define the phenotype-genotype correlation more precisely. We reported on two patients including the first prenatal case described so far, carrying a 2p15 deletion affecting two genes: XPO1 and part of USP34. Both patients shared similar features including facial dysmorphism and cerebral abnormalities. We considered the genes involved in the deleted segment to further understand the abnormal phenotype. The third case we described here was a 4-year-old boy with a heterozygous de novo 427 kb deletion encompassing BCL11A and PAPOLG at 2p16.1. He displayed speech delay, autistic traits, and motor stereotypies associated with brain structure abnormalities. We discuss the contribution of the genes included in the deletion to the abnormal phenotype. Our three new patients compared to previous cases, highlighted that despite two critical regions, both distal deletion at 2p16.1 and proximal deletion at 2p15 are associated with phenotypes that are very close to each other. Finally, we also discuss the genetic counseling of this microdeletion syndrome particularly in the course of prenatal diagnosis.

show abstract

The Novel GTPase Rit Differentially Regulates Axonal and Dendritic Growth

Cited by 53 publications

References 69 publications

RIT1 GTPase Regulates Sox2 Transcriptional Activity and Hippocampal Neurogenesis

RIT1 GTPase Regulates Sox2 Transcriptional Activity and Hippocampal Neurogenesis

Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

Molecular and clinical delineation of 2p15p16.1 microdeletion syndrome

Contact Info

Product

Resources

About