scholarly journals P470Microtubule plus-end tracking protein complex: a novel pharmacological target for modulating Nav1.5 trafficking and function

2018 ◽  
Vol 114 (suppl_1) ◽  
pp. S113-S113
Author(s):  
G A Marchal ◽  
V Portero ◽  
S Casini ◽  
A O Verkerk ◽  
N Galjart ◽  
...  
Keyword(s):  
Protein Complex ◽  
Pharmacological Target ◽  
And Function

scholarly journals Retromer subunit, VPS29, regulates synaptic transmission and is required for endolysosomal function in the aging brain

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Hui Ye ◽  
Shamsideen A Ojelade ◽  
David Li-Kroeger ◽  
Zhongyuan Zuo ◽  
Liping Wang ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Protein Complex ◽  
Adult Brain ◽  
Aging Brain ◽  
Gtpase Activating Protein ◽  
Ultrastructural Evidence ◽  
Aging Adults ◽  
And Function ◽  
Brain Homeostasis

Retromer, including Vps35, Vps26, and Vps29, is a protein complex responsible for recycling proteins within the endolysosomal pathway. Although implicated in both Parkinson’s and Alzheimer’s disease, our understanding of retromer function in the adult brain remains limited, in part because Vps35 and Vps26 are essential for development. In Drosophila, we find that Vps29 is dispensable for embryogenesis but required for retromer function in aging adults, including for synaptic transmission, survival, and locomotion. Unexpectedly, in Vps29 mutants, Vps35 and Vps26 proteins are normally expressed and associated, but retromer is mislocalized from neuropil to soma with the Rab7 GTPase. Further, Vps29 phenotypes are suppressed by reducing Rab7 or overexpressing the GTPase activating protein, TBC1D5. With aging, retromer insufficiency triggers progressive endolysosomal dysfunction, with ultrastructural evidence of impaired substrate clearance and lysosomal stress. Our results reveal the role of Vps29 in retromer localization and function, highlighting requirements for brain homeostasis in aging.

scholarly journals Assembly of a membrane receptor complex: roles of the uroplakin II prosequence in regulating uroplakin bacterial receptor oligomerization

2008 ◽  
Vol 414 (2) ◽  
pp. 195-203 ◽  
Author(s):  
Chih-Chi Andrew Hu ◽  
Thomas Bachmann ◽  
Ge Zhou ◽  
Feng-Xia Liang ◽  
Jorge Ghiso ◽  
...  
Keyword(s):  
Protein Complex ◽  
Permeability Barrier ◽  
Crystal Formation ◽  
Apical Surface ◽  
Two Dimensional ◽  
Receptor Oligomerization ◽  
Immature Form ◽  
Tract Infections ◽  
And Function ◽  
Golgi Network

The apical surface of the mammalian urothelium is almost completely covered by two-dimensional protein crystals (known as urothelial plaques) of hexagonally packed 16 nm particles consisting of two UP (uroplakin) heterodimers, i.e. UPs Ia/II and Ib/III pairs. UPs are functionally important as they contribute to the urothelial permeability barrier function, and UPIa may serve as the receptor for the uropathogenic Escherichia coli that causes over 90% of urinary tract infections. We study here how the UP proteins are assembled and targeted to the urothelial apical surface, paying special attention to the roles of the prosequence of UPII in UP oligomerization. We show that (i) the formation of the UPIa/UPII heterodimer, necessary for ER (endoplasmic reticulum) exit, requires disulfide formation in the prosequence domain of proUPII (the immature form of UPII still containing its prosequence); (ii) differentiation-dependent N-glycosylation of the prosequence leads to UP stabilization; (iii) a failure to form tetramers in cultured urothelial cells, in part due to altered glycosylation of the prosequence, may block two-dimensional crystal formation; and (iv) the prosequence of UPII remains attached to the mature protein complex on the urothelial apical surface even after it has been cleaved by the trans-Golgi-network-associated furin. Our results indicate that proper secondary modifications of the prosequence of UPII play important roles in regulating the oligomerization and function of the UP protein complex.

scholarly journals Vac14 Protein Multimerization Is a Prerequisite Step for Fab1 Protein Complex Assembly and Function

2013 ◽  
Vol 288 (13) ◽  
pp. 9363-9372 ◽  
Author(s):  
Tamadher A. Alghamdi ◽  
Cheuk Y. Ho ◽  
Amra Mrakovic ◽  
Danielle Taylor ◽  
Daniel Mao ◽  
...  
Keyword(s):  
Protein Complex ◽  
Complex Assembly ◽  
Protein Multimerization ◽  
And Function ◽  
Protein Complex Assembly

Uptake of Polynucleotides by Mammalian Cells XV. Properties and Function of a DNA-Protein Complex Situated in the Outer Membrane of Ehrlich Ascites Tumor Cells

1978 ◽  
Vol 33 (1-2) ◽  
pp. 96-104 ◽  
Author(s):  
P. L. Schell
Keyword(s):  
Protein Complex ◽  
Mammalian Cells ◽  
Protein Complexes ◽  
Protein Structures ◽  
Uptake Capacity ◽  
Viable Cells ◽  
Ehrlich Ascites ◽  
Protease Treatment ◽  
And Function

Abstract 1) DNA-protein complexes are supposed to be original constituents of the membrane of Ehrlich ascites tum or cells. These complexes can be attacked at the surface of viable cells by DNase or protease. The DNA is partially embedded in protein structures.2) The net charge of this complex is of major importance for the RNA uptake capacity of the cells. Negatively charged DNA which is situated at the surface hinders RNA uptake. This is the explanation for the stimulation of RNA uptake by DNase or the decrease in RNA uptake after protease treatment.3) Upon treatment of DNA-dcficient complexes with homologous or heterologous DNA the original RNA uptake capacity of the cells is restored but the original conformation of the complex cannot be regained.4) The DNase action on the complex is tem perature dependent in a sigmoidal fashion. It is m arkedly slowed down at tem peratures below 12 °C. This implies that structural dianges in the complex occur at this transition tem perature which make surface DNA susceptible to DNase. This effect can only be observed in original structures but not in reconstituted ones.5) Polyanion treatment of the cells [poly (L-lysine) ] which increases their RNA uptake capacity, most probably does not interact with the DNA-protein complex. Poly (L-lysine) appears to act at other m em brane sites.6) The DNA-protein complex has been investigated entirely in situ , i. e. situated in the membrane of viable cells.

scholarly journals NuMA localization, stability, and function in spindle orientation involve 4.1 and Cdk1 interactions

2013 ◽  
Vol 24 (23) ◽  
pp. 3651-3662 ◽  
Author(s):  
Lindsey Seldin ◽  
Nicholas D. Poulson ◽  
Henry P. Foote ◽  
Terry Lechler
Keyword(s):  
Protein Complex ◽  
Fluorescence Recovery After Photobleaching ◽  
Force Generation ◽  
Spindle Orientation ◽  
Cell Cortex ◽  
Mitotic Apparatus ◽  
Productive Force ◽  
Asymmetric Divisions ◽  
And Function ◽  
Multilayered Epithelium

The epidermis is a multilayered epithelium that requires asymmetric divisions for stratification. A conserved cortical protein complex, including LGN, nuclear mitotic apparatus (NuMA), and dynein/dynactin, plays a key role in establishing proper spindle orientation during asymmetric divisions. The requirements for the cortical recruitment of these proteins, however, remain unclear. In this work, we show that NuMA is required to recruit dynactin to the cell cortex of keratinocytes. NuMA's cortical recruitment requires LGN; however, LGN interactions are not sufficient for this localization. Using fluorescence recovery after photobleaching, we find that the 4.1-binding domain of NuMA is important for stabilizing its interaction with the cell cortex. This is functionally important, as loss of 4.1/NuMA interaction results in spindle orientation defects, using two distinct assays. Furthermore, we observe an increase in cortical NuMA localization as cells enter anaphase. Inhibition of Cdk1 or mutation of a single residue in NuMA mimics this effect. NuMA's anaphase localization is independent of LGN and 4.1 interactions, revealing two distinct mechanisms responsible for NuMA cortical recruitment at different stages of mitosis. This work highlights the complexity of NuMA localization and reveals the importance of NuMA cortical stability for productive force generation during spindle orientation.

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