The primate-specific protein TBC1D3 is required for optimal macropinocytosis in a novel ARF6-dependent pathway

Molecular Biology of the Cell
Emanuela FrittoliStefano Confalonieri

Abstract

The generation of novel genes and proteins throughout evolution has been proposed to occur as a result of whole genome and gene duplications, exon shuffling, and retrotransposition events. The analysis of such genes might thus shed light into the functional complexity associated with highly evolved species. One such case is represented by TBC1D3, a primate-specific gene, harboring a TBC domain. Because TBC domains encode Rab-specific GAP activities, TBC-containing proteins are predicted to play a major role in endocytosis and intracellular traffic. Here, we show that the TBC1D3 gene originated late in evolution, likely through a duplication of the RNTRE locus, and underwent gene amplification during primate speciation. Despite possessing a TBC domain, TBC1D3 is apparently devoid of Rab-GAP activity. However, TBC1D3 regulates the optimal rate of epidermal growth factor-mediated macropinocytosis by participating in a novel pathway involving ARF6 and RAB5. In addition, TBC1D3 binds and colocalize to GGA3, an ARF6-effector, in an ARF6-dependent manner, and synergize with it in promoting macropinocytosis, suggesting that the two proteins act together in this process. Accordingly, GGA3 siRNA-mediated ablation impaired TBC1D3-induced ...Continue Reading

References

Jun 8, 1999·Annual Review of Immunology·A Aderem, D M Underhill
Jun 22, 1999·FEBS Letters·M Katan, V L Allen
Oct 12, 2000·Molecular Biology of the Cell·S DharmawardhaneG M Bokoch
Oct 20, 2000·Bioinformatics·J Bingham, S Sudarsanam
Feb 22, 2001·Science·A Courseaux, J L Nahon
Mar 29, 2001·Traffic·D A SchaferJ A Cooper
Sep 6, 2001·The Journal of Cell Biology·F D BrownJ G Donaldson
Oct 30, 2001·Current Opinion in Genetics & Development·M Long
Mar 14, 2002·International Journal of Medical Microbiology : IJMM·Mustapha AmyerePierre J Courtoy
May 29, 2002·Nature Genetics·Aoife McLysaghtKenneth H Wolfe
Jul 4, 2002·Methods in Molecular Biology·Julie G Donaldson
Aug 10, 2002·Science·Jeffrey A BaileyEvan E Eichler
Feb 27, 2003·Proceedings of the National Academy of Sciences of the United States of America·Charles A PauldingDaniel A Haber
Mar 7, 2003·Nature·Sean D Conner, Sandra L Schmid
Oct 3, 2003·Biochemical and Biophysical Research Communications·Christelle BizimunguMicheline Vandenbol
Jan 7, 2004·Nature Reviews. Molecular Cell Biology·Juan S Bonifacino
Nov 1, 1995·Trends in Cell Biology·J A Swanson, C Watts
Mar 25, 2004·Nature Cell Biology·Rosa Puertollano, Juan S Bonifacino
Jun 9, 2004·Trends in Cell Biology·Theresia E B StradalGiorgio Scita
Sep 16, 2004·Nature Reviews. Molecular Cell Biology·Roberto BuccioneMark A McNiven
Dec 1, 2004·Annual Review of Genetics·John S Taylor, Jeroen Raes
Jun 24, 2005·The Biochemical Journal·Cristinel P MîineaGustav E Lienhard
Jul 27, 2005·Biochemical Society Transactions·J G Donaldson, A Honda
Aug 2, 2005·Biochemical and Biophysical Research Communications·Xiang-Ming ZhangTony Rowe
Aug 9, 2005·Nature Cell Biology·Alexander K HaasFrancis A Barr
Sep 13, 2005·Nature Cell Biology·Metello InnocentiGiorgio Scita
Oct 26, 2005·Biochemical Society Transactions·J G Donaldson
Nov 16, 2005·Annual Review of Genetics·Eugene V Koonin
Nov 18, 2005·Current Opinion in Structural Biology·Masato KawasakiSoichi Wakatsuki
Dec 31, 2005·Nucleic Acids Research·Ivica LetunicPeer Bork

❮ Previous
Next ❯

Citations

Jan 19, 2012·Nature Reviews. Molecular Cell Biology·Marieke A M FrasaVania M M Braga
Aug 10, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ragna SannerudWim Annaert
Mar 6, 2008·The Journal of Biological Chemistry·Marisa J WainszelbaumPhilip D Stahl
Oct 3, 2009·Science Signaling·Philip D Stahl, Marisa J Wainszelbaum
Nov 14, 2013·BMC Infectious Diseases·Eleni AklilluEdward J Hollox
Nov 15, 2008·PloS One·Katia CorteseFrancesco Blasi
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Claudia M B CarvalhoJames R Lupski
Jan 13, 2010·The Journal of Cell Biology·Christopher EskFrances M Brodsky
Jul 17, 2015·International Journal of Molecular Medicine·Julian Banerji
Dec 17, 2008·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Koutaro IshibashiMitsunori Fukuda
Jan 22, 2011·Bioscience Reports·Mitsunori Fukuda
Jul 17, 2012·Molecular Cell·Christian C DibbleBrendan D Manning
Apr 13, 2013·Biochemical and Biophysical Research Communications·Chen KongPhilip D Stahl
Feb 15, 2016·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Andrew BairdBrian P Eliceiri
Sep 25, 2016·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Andrew BairdBrian P Eliceiri
Sep 19, 2019·Briefings in Functional Genomics·Cemalettin Bekpen, Diethard Tautz
Feb 5, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shu QinBrian P Eliceiri
Apr 11, 2019·Molecular Biology of the Cell·Chad D Williamson, Julie G Donaldson
Apr 11, 2019·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Joel A Swanson, Sei Yoshida
Jul 15, 2017·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Mattéa J Finelli, Peter L Oliver

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.