Intracellular Transport and Kinesin Superfamily Proteins, KIFs: Structure, Function, and Dynamics

2008 ◽  
Vol 88 (3) ◽  
pp. 1089-1118 ◽  
Author(s):  
Nobutaka Hirokawa ◽  
Yasuko Noda
Keyword(s):  
Cell Biology ◽  
Intracellular Transport ◽  
Structural Changes ◽  
Motor Proteins ◽  
Protein Complexes ◽  
Molecular Genetic ◽  
Adaptor Protein ◽  
Binding Activity ◽  
Brain Functions ◽  
Kinesin Superfamily

Various molecular cell biology and molecular genetic approaches have indicated significant roles for kinesin superfamily proteins (KIFs) in intracellular transport and have shown that they are critical for cellular morphogenesis, functioning, and survival. KIFs not only transport various membrane organelles, protein complexes, and mRNAs for the maintenance of basic cellular activity, but also play significant roles for various mechanisms fundamental for life, such as brain wiring, higher brain functions such as memory and learning and activity-dependent neuronal survival during brain development, and for the determination of important developmental processes such as left-right asymmetry formation and suppression of tumorigenesis. Accumulating data have revealed a molecular mechanism of cargo recognition involving scaffolding or adaptor protein complexes. Intramolecular folding and phosphorylation also regulate the binding activity of motor proteins. New techniques using molecular biophysics, cryoelectron microscopy, and X-ray crystallography have detected structural changes in motor proteins, synchronized with ATP hydrolysis cycles, leading to the development of independent models of monomer and dimer motors for processive movement along microtubules.

Kinesin superfamily motor proteins and intracellular transport

2009 ◽  
Vol 10 (10) ◽  
pp. 682-696 ◽  
Author(s):  
Nobutaka Hirokawa ◽  
Yasuko Noda ◽  
Yosuke Tanaka ◽  
Shinsuke Niwa
Keyword(s):  
Intracellular Transport ◽  
Motor Proteins ◽  
Kinesin Superfamily

scholarly journals Adaptor protein complexes and intracellular transport

2014 ◽  
Vol 34 (4) ◽  
Author(s):  
Sang Yoon Park ◽  
Xiaoli Guo
Keyword(s):  
Membrane Trafficking ◽  
Intracellular Transport ◽  
Protein Complexes ◽  
Adaptor Protein ◽  
Inherited Disorders ◽  
Transport Pathways ◽  
Vesicular Carriers ◽  
Cargo Proteins ◽  
Intracellular Compartments ◽  
Secretory Transport

The AP (adaptor protein) complexes are heterotetrameric protein complexes that mediate intracellular membrane trafficking along endocytic and secretory transport pathways. There are five different AP complexes: AP-1, AP-2 and AP-3 are clathrin-associated complexes; whereas AP-4 and AP-5 are not. These five AP complexes localize to different intracellular compartments and mediate membrane trafficking in distinct pathways. They recognize and concentrate cargo proteins into vesicular carriers that mediate transport from a donor membrane to a target organellar membrane. AP complexes play important roles in maintaining the normal physiological function of eukaryotic cells. Dysfunction of AP complexes has been implicated in a variety of inherited disorders, including: MEDNIK (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis and keratodermia) syndrome, Fried syndrome, HPS (Hermansky–Pudlak syndrome) and HSP (hereditary spastic paraplegia).

ARFGAP3 an androgen target gene promotes prostate cancer cell proliferation and migration.

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
Cell Biology ◽  
Adaptor Protein ◽  
Cancer Cell Proliferation ◽  
Lncap Cells ◽  
Gtpase Activating Protein ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

ADP ribosylation factor GTPase-activating protein 3 (ARFGAP3) is a GTPase-activating protein that associates with the Golgiapparatus and regulates the vesicular trafficking pathway. In the present study, we examined the contribution of ARFGAP3 toprostate cancer cell biology. We showed that ARFGAP3 expression was induced by 100 nM of dihydrotestosterone (DHT) atboth the mRNA and protein levels in androgen-sensitive LNCaP cells. We generated stable transfectants of LNCaP cells withFLAG-tagged ARFGAP3 or a control empty vector and showed that ARFGAP3 overexpression promoted cell proliferation andmigration compared with control cells. We found that ARFGAP3 interacted with paxillin, a focal adhesion adaptor protein thatis important for cell mobility and migration. Small interfering RNA (siRNA)-mediated knockdown of ARFGAP3 showed thatARFGAP3 siRNA markedly reduced LNCaP cell growth. Androgen receptor (AR)-dependent transactivation activity on prostatespecificantigen (PSA) enhancer was synergistically promoted by exogenous ARFGAP3 and paxillin expression, as shown byluciferase assay in LNCaP cells. Thus, our results suggest that ARFGAP3 is a novel androgen-regulated gene that can promoteprostate cancer cell proliferation and migration in collaboration with paxillin.

Breeding study of sea buckthorn (Hippophae rhamnoides L.) in the Institute of Horticulture, NAAS оf Ukraine

2020 ◽  
pp. 37-49
Author(s):  
V.V. Moskalets ◽  
◽  
T.Z. Moskalets ◽  
I.V. Grynyk ◽  
O.A. Shevchuk ◽  
...  
Keyword(s):  
Genetic Markers ◽  
Cell Biology ◽  
Molecular Genetic ◽  
The State ◽  
Sea Buckthorn ◽  
National Academy Of Sciences ◽  
Scientific Cooperation ◽  
State Register ◽  
Academy Of Sciences

The authors present the results of the sea buckthorn breeding at the Institute of Horticulture (NAAS). The stages of the work have been analyzed – from studying and selecting the initial material in the conditions of the Polissya, Polissya-Lisosteppe and Lisosteppe ecotopes (2012-2016) to the successful targeted introduction to the Northern part of the Lisosteppe (2017-2019) and new forms have been characterized according to the traits valuable for economy and molec-ular genetic markers. The new forms of the researched crop taking into consideration the high indices of their productiv-ity,adaptivity to the unfavourable abiotic and biotic environmental factors and consumption quality of fruits for pro-cessing and making functionary products were entered officially into Genetic Fund of the Plants of Ukraine as con-firmed by the certificates of copyright and developed genetic passports. The list of these genotypes includes 1-15-1 (Nos-ivchanka, UA3700073), 1-15-8S (Mitsna, UA3700079), make form 1-15-6Ch (Aboryhen 6/11, UA3700080), 1-15-9 Ka-rotynna, UA3700082), 1-15-3 (Pamiatka, UA3700076), 1-15-8V (Soniachne siayvo, UA3700075), 1-15-11 (Lymonna, UA3700072), 2-15-73 (Morkviana, UA3700077), 1-15-5 (Adaptyvna, UA3700078), 1-15-8B (Osoblyva, UA3700083), 1-15-6 (Apelsynova, UA3700084) and forms 6A/11 (UA3700081), 1-15-5a (Sribnolysta 5a, UA3700074). The possibility of using 5 DNA markers to characterize genotypes of sea buckthorn bymeans of the molecular genetic markers was tested and evaluated in the framework of the scientific cooperation with the Institute of Cell Biology and Genetic Engineering of the National Academy of Sciences of Ukraine. It should be noted that the most polymorphic markers were HrMS025 and HrMS026. However, the marker HrMS014 was monomorphic, but appeared in all the samples, so it can be used as a reference. The best forms of sea buckthorn Adaptyvna (certificate №190899) and Osoblyva (certificate №190900) were included into the State Register of Plant Varieties Suitable for dissemination in Ukraine, and the cultivars of the univer-sal use Nadiina (applications №18299010), Oliana (applications №18299009) and Morkviana (applications № 20299001) and cv pollinator Obrii (applications №18299008) undergo the State strain test. The attention is concentrat-ed on the promising directions of the new sea buckthorn genotypes for the prior breeding and genetic investigations at the Institute of Horticulture (NAAS) and its network.

scholarly journals Fundamental functional differences between gyri and sulci: implications for brain function, cognition, and behavior

2021 ◽  
Vol 1 (1) ◽  
pp. 23-41
Author(s):  
Xi Jiang ◽  
Tuo Zhang ◽  
Shu Zhang ◽  
Keith M Kendrick ◽  
Tianming Liu
Keyword(s):  
Brain Function ◽  
Cell Biology ◽  
Functional Anatomy ◽  
Building Blocks ◽  
Functional Differentiation ◽  
Cortical Folding ◽  
Brain Functions ◽  
Functional Relationships ◽  
Structural Architecture ◽  
And Behavior

Abstract Folding of the cerebral cortex is a prominent characteristic of mammalian brains. Alterations or deficits in cortical folding are strongly correlated with abnormal brain function, cognition, and behavior. Therefore, a precise mapping between the anatomy and function of the brain is critical to our understanding of the mechanisms of brain structural architecture in both health and diseases. Gyri and sulci, the standard nomenclature for cortical anatomy, serve as building blocks to make up complex folding patterns, providing a window to decipher cortical anatomy and its relation with brain functions. Huge efforts have been devoted to this research topic from a variety of disciplines including genetics, cell biology, anatomy, neuroimaging, and neurology, as well as involving computational approaches based on machine learning and artificial intelligence algorithms. However, despite increasing progress, our understanding of the functional anatomy of gyro-sulcal patterns is still in its infancy. In this review, we present the current state of this field and provide our perspectives of the methodologies and conclusions concerning functional differentiation between gyri and sulci, as well as the supporting information from genetic, cell biology, and brain structure research. In particular, we will further present a proposed framework for attempting to interpret the dynamic mechanisms of the functional interplay between gyri and sulci. Hopefully, this review will provide a comprehensive summary of anatomo-functional relationships in the cortical gyro-sulcal system together with a consideration of how these contribute to brain function, cognition, and behavior, as well as to mental disorders.

scholarly journals Stoichiometry and Turnover of the Bacterial Flagellar Switch Protein FliN

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Nicolas J. Delalez ◽  
Richard M. Berry ◽  
Judith P. Armitage
Keyword(s):  
Copy Number ◽  
Motor Proteins ◽  
Fluorescent Protein ◽  
Protein Complexes ◽  
Content Type ◽  
Rotation Direction ◽  
Cell Measurement ◽  
Biological Complexes ◽  
And Function

ABSTRACTSome proteins in biological complexes exchange with pools of free proteins while the complex is functioning. Evidence is emerging that protein exchange can be part of an adaptive mechanism. The bacterial flagellar motor is one of the most complex biological machines and is an ideal model system to study protein dynamics in large multimeric complexes. Recent studies showed that the copy number of FliM in the switch complex and the fraction of FliM that exchanges vary with the direction of flagellar rotation. Here, we investigated the stoichiometry and turnover of another switch complex component, FliN, labeled with the fluorescent protein CyPet, inEscherichia coli. Our results confirm that,in vivo, FliM and FliN form a complex with stoichiometry of 1:4 and function as a unit. We estimated that wild-type motors contained 120 ± 26 FliN molecules. Motors that rotated only clockwise (CW) or counterclockwise (CCW) contained 114 ± 17 and 144 ± 26 FliN molecules, respectively. The ratio of CCW-to-CW FliN copy numbers was 1.26, very close to that of 1.29 reported previously for FliM. We also measured the exchange of FliN molecules, which had a time scale and dependence upon rotation direction similar to those of FliM, consistent with an exchange of FliM-FliN as a unit. Our work confirms the highly dynamic nature of multimeric protein complexes and indicates that, under physiological conditions, these machines might not be the stable, complete structures suggested by averaged fixed methodologies but, rather, incomplete rings that can respond and adapt to changing environments.IMPORTANCEThe flagellum is one of the most complex structures in a bacterial cell, with the core motor proteins conserved across species. Evidence is now emerging that turnover of some of these motor proteins depends on motor activity, suggesting that turnover is important for function. The switch complex transmits the chemosensory signal to the rotor, and we show, by using single-cell measurement, that both the copy number and the fraction of exchanging molecules vary with the rotational bias of the rotor. When the motor is locked in counterclockwise rotation, the copy number is similar to that determined by averaged, fixed methodologies, but when locked in a clockwise direction, the number is much lower, suggesting that that the switch complex ring is incomplete. Our results suggest that motor remodeling is an important component in tuning responses and adaptation at the motor.

scholarly journals Proteomic insights into synaptic signaling in the brain: the past, present and future

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yalan Xu ◽  
Xiuyue Song ◽  
Dong Wang ◽  
Yin Wang ◽  
Peifeng Li ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Protein Complexes ◽  
Synaptic Signaling ◽  
Brain Functions ◽  
The Past ◽  
Data Independent Acquisition ◽  
Technological Advances ◽  
Neural Communication ◽  
Chemical Synapses ◽  
The Brain

AbstractChemical synapses in the brain connect neurons to form neural circuits, providing the structural and functional bases for neural communication. Disrupted synaptic signaling is closely related to a variety of neurological and psychiatric disorders. In the past two decades, proteomics has blossomed as a versatile tool in biological and biomedical research, rendering a wealth of information toward decoding the molecular machinery of life. There is enormous interest in employing proteomic approaches for the study of synapses, and substantial progress has been made. Here, we review the findings of proteomic studies of chemical synapses in the brain, with special attention paid to the key players in synaptic signaling, i.e., the synaptic protein complexes and their post-translational modifications. Looking toward the future, we discuss the technological advances in proteomics such as data-independent acquisition mass spectrometry (DIA-MS), cross-linking in combination with mass spectrometry (CXMS), and proximity proteomics, along with their potential to untangle the mystery of how the brain functions at the molecular level. Last but not least, we introduce the newly developed synaptomic methods. These methods and their successful applications marked the beginnings of the synaptomics era.

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