scholarly journals Novel defect in phosphatidylinositol 4‐kinase type 2‐alpha ( PI4K2A ) at the membrane‐enzyme interface is associated with metabolic cutis laxa

2020 ◽  
Vol 43 (6) ◽  
pp. 1382-1391
Author(s):  
Miski Mohamed ◽  
Thatjana Gardeitchik ◽  
Shanti Balasubramaniam ◽  
Sergio Guerrero‐Castillo ◽  
Daisy Dalloyaux ◽  
...  
Keyword(s):  
Cutis Laxa ◽  
Membrane Enzyme ◽  
Phosphatidylinositol 4

Autosomal Recessive Cutis Laxa Type 2

2009 ◽  
pp. 196-197
Author(s):  
Hubert Scharnagl ◽  
Winfried März ◽  
Markus Böhm ◽  
Thomas A. Luger ◽  
Federico Fracassi ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Cutis Laxa

scholarly journals Mutations in PYCR1 gene in three families with autosomal recessive cutis laxa, type 2

2013 ◽  
Vol 56 (6) ◽  
pp. 336-339 ◽  
Author(s):  
D.Z. Scherrer ◽  
M.B. Baptista ◽  
A.H.B. Matos ◽  
C.V. Maurer-Morelli ◽  
C.E. Steiner
Keyword(s):  
Autosomal Recessive ◽  
Cutis Laxa

scholarly journals Study of the polymorphic variants of the PIP5K2A gene association with the comorbidity of alcoholism and affective disorders

2019 ◽  
pp. 124-126
Author(s):  
E. V. Mikhalitskaya ◽  
O. V. Roshchina ◽  
S. A. Ivanova ◽  
N. A. Bokhan
Keyword(s):  
Alcohol Dependence ◽  
Depressive Disorders ◽  
Neuronal Excitability ◽  
Control Group ◽  
Genotype Distribution ◽  
Patient Groups ◽  
The Common ◽  
Polymorphic Variants ◽  
Phosphatidylinositol 4

One of the common pathogenetic mechanisms of the formation of alcohol dependence and depressive disorders can be a violation of the neurotransmitter systems, in particular — dopamine. Phosphatidylinositol-4-phosphate-5-kinase type 2 alpha (PIP5K2A) plays an important role in the regulation of neuronal excitability and synaptic dopamine neurotransmission. The aim of this study was to assess the presence of associations of the PIP5K2A gene polymorphic variants with the comorbid course of alcohol dependence and depressive disorders. This study showed differences in the frequency of the genotype distribution of 3 PIP5K2A gene polymorphisms (rs946961, rs1132816, and rs1417374) both between patient groups compared with the control group, and between the patient group and the group with the comorbid course of disorders.

scholarly journals The PI(4)P phosphatase Sac2 controls insulin granule docking and release

2019 ◽  
Vol 218 (11) ◽  
pp. 3714-3729 ◽  
Author(s):  
Phuoc My Nguyen ◽  
Nikhil R. Gandasi ◽  
Beichen Xie ◽  
Sari Sugahara ◽  
Yingke Xu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Membrane ◽  
Insulin Secretion ◽  
Dependent Manner ◽  
Impaired Insulin Secretion ◽  
Insulin Granules ◽  
Impaired Insulin ◽  
Insulin Granule ◽  
Phosphatidylinositol 4

Insulin granule biogenesis involves transport to, and stable docking at, the plasma membrane before priming and fusion. Defects in this pathway result in impaired insulin secretion and are a hallmark of type 2 diabetes. We now show that the phosphatidylinositol 4-phosphate phosphatase Sac2 localizes to insulin granules in a substrate-dependent manner and that loss of Sac2 results in impaired insulin secretion. Sac2 operates upstream of granule docking, since loss of Sac2 prevented granule tethering to the plasma membrane and resulted in both reduced granule density and number of exocytic events. Sac2 levels correlated positively with the number of docked granules and exocytic events in clonal β cells and with insulin secretion in human pancreatic islets, and Sac2 expression was reduced in islets from type 2 diabetic subjects. Taken together, we identified a phosphoinositide switch on the surface on insulin granules that is required for stable granule docking at the plasma membrane and impaired in human type 2 diabetes.

scholarly journals Two phosphatidylinositol 4-kinases control lysosomal delivery of the Gaucher disease enzyme, β-glucocerebrosidase

2012 ◽  
Vol 23 (8) ◽  
pp. 1533-1545 ◽  
Author(s):  
Marko Jović ◽  
Michelle J. Kean ◽  
Zsofia Szentpetery ◽  
Gordon Polevoy ◽  
Anne-Claude Gingras ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Lysosomal Storage Disorder ◽  
Integral Membrane Protein ◽  
Lysosomal Storage ◽  
Trafficking Pathway ◽  
Golgi Compartment ◽  
Phosphatidylinositol 4 ◽  
Endosomal Vesicles ◽  
Membrane Protein Type

Gaucher disease is a lysosomal storage disorder caused by a defect in the degradation of glucosylceramide catalyzed by the lysosomal enzyme β-glucocerebrosidase (GBA). GBA reaches lysosomes via association with its receptor, lysosomal integral membrane protein type 2 (LIMP-2). We found that distinct phosphatidylinositol 4-kinases (PI4Ks) play important roles at multiple steps in the trafficking pathway of the LIMP-2/GBA complex. Acute depletion of phosphatidylinositol 4-phosphate in the Golgi caused accumulation of LIMP-2 in this compartment, and PI4KIIIβ was found to be responsible for controlling the exit of LIMP-2 from the Golgi. In contrast, depletion of PI4KIIα blocked trafficking at a post-Golgi compartment, leading to accumulation of LIMP-2 in enlarged endosomal vesicles. PI4KIIα depletion also caused secretion of missorted GBA into the medium, which was attenuated by limiting LIMP-2/GBA exit from the Golgi by PI4KIIIβ inhibitors. These studies identified PI4KIIIβ and PI4KIIα as important regulators of lysosomal delivery of GBA, revealing a new element of control to sphingolipid homeostasis by phosphoinositides.

scholarly journals Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate

2015 ◽  
Vol 209 (3) ◽  
pp. 435-452 ◽  
Author(s):  
Pehuén Pereyra Gerber ◽  
Mercedes Cabrini ◽  
Carolina Jancic ◽  
Luciana Paoletti ◽  
Claudia Banchio ◽  
...  
Keyword(s):  
T Cells ◽  
Plasma Membrane ◽  
Cd4 T Cells ◽  
Membrane Association ◽  
Late Endosomes ◽  
Phosphatidylinositol 4 ◽  
Viral Polyprotein ◽  
Late Stages ◽  
Hiv 1

During the late stages of the HIV-1 replication cycle, the viral polyprotein Pr55Gag is recruited to the plasma membrane (PM), where it binds phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and directs HIV-1 assembly. We show that Rab27a controls the trafficking of late endosomes carrying phosphatidylinositol 4-kinase type 2 α (PI4KIIα) toward the PM of CD4+ T cells. Hence, Rab27a promotes high levels of PM phosphatidylinositol 4-phosphate and the localized production of PI(4,5)P2, therefore controlling Pr55Gag membrane association. Rab27a also controls PI(4,5)P2 levels at the virus-containing compartments of macrophages. By screening Rab27a effectors, we identified that Slp2a, Slp3, and Slac2b are required for the association of Pr55Gag with the PM and that Slp2a cooperates with Rab27a in the recruitment of PI4KIIα to the PM. We conclude that by directing the trafficking of PI4KIIα-positive endosomes toward the PM, Rab27a controls PI(4,5)P2 production and, consequently, HIV-1 replication.

scholarly journals Mutation in Pyrroline-5-Carboxylate Reductase 1 Gene in Families with Cutis Laxa Type 2

2009 ◽  
Vol 85 (1) ◽  
pp. 120-129 ◽  
Author(s):  
Duane L. Guernsey ◽  
Haiyan Jiang ◽  
Susan C. Evans ◽  
Meghan Ferguson ◽  
Makoto Matsuoka ◽  
...  
Keyword(s):  
Cutis Laxa ◽  
Carboxylate Reductase
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