P-Type Lectins and Lysosomal Enzyme Trafficking

McKusick subdivided the syndrome of mucopolysaccharidoses into six types according to clinical, roentenographic, and genetic criteria and to the kind of mucopolysaccharide(s) excreted in the urine (1). Deficient activity of a lysosomal enzyme, (β-galactosidase, has recently been reported in types I, II and III of mucopolysaccharidoses as well as in generalized gangliosidosis (2). This apparent lack of disease specificity makes the enzymatic deficiency difficult to interpret. Nevertheless, the involvement of a lysosomal enzyme tends to characterize these disorders as lysosomal diseases.

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Interface morphology of thermal oxide grown on polycrystalline silicon by different processes

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100131619 ◽

1992 ◽

Vol 50 (2) ◽

pp. 1396-1397

Author(s):

H. Yen ◽

E. P. Kvam ◽

R. Bashir ◽

S. Venkatesan ◽

G. W. Neudeck

Keyword(s):

Integrated Circuits ◽

Polycrystalline Silicon ◽

Silicon Films ◽

Interface Morphology ◽

Oxide Interface ◽

Poly Silicon ◽

Thermal Oxide ◽

Grain Orientations ◽

Polycrystalline Silicon Films ◽

P Type

Polycrystalline silicon, when highly doped, is commonly used in microelectronics applications such as gates and interconnects. The packing density of integrated circuits can be enhanced by fabricating multilevel polycrystalline silicon films separated by insulating SiO2 layers. It has been found that device performance and electrical properties are strongly affected by the interface morphology between polycrystalline silicon and SiO2. As a thermal oxide layer is grown, the poly silicon is consumed, and there is a volume expansion of the oxide relative to the atomic silicon. Roughness at the poly silicon/thermal oxide interface can be severely deleterious due to stresses induced by the volume change during oxidation. Further, grain orientations and grain boundaries may alter oxidation kinetics, which will also affect roughness, and thus stress.Three groups of polycrystalline silicon films were deposited by LPCVD after growing thermal oxide on p-type wafers. The films were doped with phosphorus or arsenic by three different methods.

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Determination of arsenic atom distribution arsenic doped silicon using HOLZ-line analysis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100167342 ◽

1996 ◽

Vol 54 ◽

pp. 976-977

Author(s):

Y. Kikuchi ◽

N. Hashikawa ◽

F. Uesugi ◽

E. Wakai ◽

K. Watanabe ◽

...

Keyword(s):

Inelastic Scattering ◽

Zone Axis ◽

Experimental Result ◽

Background Intensity ◽

Crystal Thickness ◽

Arsenic Atom ◽

Doped Silicon ◽

P Type ◽

Line Analysis

In order to measure the concentration of arsenic atoms in nanometer regions of arsenic doped silicon, the HOLZ analysis is carried out underthe exact [011] zone axis observation. In previous papers, it is revealed that the position of two bright lines in the outer SOLZ structures on the[011] zone axis is little influenced by the crystal thickness and the background intensity caused by inelastic scattering electrons, but is sensitive to the concentration of As atoms substitutbnal for Siatomic site.As the result, it becomes possible to determine the concentration of electrically activated As atoms in silicon within an observed area by means of the simple fitting between experimental result and dynamical simulatioan. In the present work, in order to investigate the distribution of electrically activated As in silicon, the outer HOLZ analysis is applied using a nanometer sized probe of TEM equipped with a FEG.Czodiralsld-gown<100>orientated p-type Si wafers with a resistivity of 10 Ώ cm are used for the experiments.TheAs+ implantation is performed at a dose of 5.0X1015cm-2at 25keV.

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Electron Microscopy in the diagnosis of lysosomal storage diseases

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100156316 ◽

1989 ◽

Vol 47 ◽

pp. 866-867

Author(s):

Carole Vogler ◽

Harvey S. Rosenberg

Keyword(s):

Electron Microscopy ◽

Lysosomal Enzyme ◽

Rectal Mucosa ◽

Lysosomal Storage Diseases ◽

Cell Types ◽

Lysosomal Storage ◽

Storage Material ◽

Ultrastructural Examination ◽

Blood Leukocytes ◽

Storage Diseases

Diagnostic procedures for evaluation of patients with lysosomal storage diseases (LSD) seek to identify a deficiency of a responsible lysosomal enzyme or accumulation of a substance that requires the missing enzyme for degradation. Most patients with LSD have progressive neurological degeneration and may have a variety of musculoskeletal and visceral abnormalities. In the LSD, the abnormally diminished lysosomal enzyme results in accumulation of unmetabolized catabolites in distended lysosomes. Because of the subcellular morphology and size of lysosomes, electron microscopy is an ideal tool to study tissue from patients with suspected LSD. In patients with LSD all cells lack the specific lysosomal enzyme but the distribution of storage material is dependent on the extent of catabolism of the substrate in each cell type under normal circumstances. Lysosmal storages diseases affect many cell types and tissues. Storage material though does not accumulate in all tissues and cell types and may be different biochemically and morphologically in different tissues.Conjunctiva, skin, rectal mucosa and peripheral blood leukocytes may show ultrastructural evidence of lysosomal storage even in the absence of clinical findings and thus any of these tissues can be used for ultrastructural examination in the diagnostic evaluation of patients with suspected LSD. Biopsy of skin and conjunctiva are easily obtained and provide multiple cell types including endothelium, epithelium, fibroblasts and nerves for ultrastructural study. Fibroblasts from skin and conjunctiva can also be utilized for the initiation of tissue cultures for chemical assays. Brain biopsy has been largely replaced by biopsy of more readily obtained tissue and by biochemical assays. Such assays though may give equivical or nondiagnostic results and in some lysosomal storage diseases an enzyme defect has not yet been identified and diagnoses can be made only by ultrastructural examination.

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Investigating the functional link between TMEM165 and SPCA1

Biochemical Journal ◽

10.1042/bcj20190488 ◽

2019 ◽

Vol 476 (21) ◽

pp. 3281-3293 ◽

Cited By ~ 2

Author(s):

Elodie Lebredonchel ◽

Marine Houdou ◽

Hans-Heinrich Hoffmann ◽

Kateryna Kondratska ◽

Marie-Ange Krzewinski ◽

...

Keyword(s):

Subcellular Localization ◽

Complete Loss ◽

Protein Family ◽

Uncharacterized Protein ◽

Functional Link ◽

P Type

TMEM165 was highlighted in 2012 as the first member of the Uncharacterized Protein Family 0016 (UPF0016) related to human glycosylation diseases. Defects in TMEM165 are associated with strong Golgi glycosylation abnormalities. Our previous work has shown that TMEM165 rapidly degrades with supraphysiological manganese supplementation. In this paper, we establish a functional link between TMEM165 and SPCA1, the Golgi Ca2+/Mn2+ P-type ATPase pump. A nearly complete loss of TMEM165 was observed in SPCA1-deficient Hap1 cells. We demonstrate that TMEM165 was constitutively degraded in lysosomes in the absence of SPCA1. Complementation studies showed that TMEM165 abundance was directly dependent on SPCA1's function and more specifically its capacity to pump Mn2+ from the cytosol into the Golgi lumen. Among SPCA1 mutants that differentially impair Mn2+ and Ca2+ transport, only the Q747A mutant that favors Mn2+ pumping rescues the abundance and Golgi subcellular localization of TMEM165. Interestingly, the overexpression of SERCA2b also rescues the expression of TMEM165. Finally, this paper highlights that TMEM165 expression is linked to the function of SPCA1.

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Structural dynamics of P-type ATPase ion pumps

Biochemical Society Transactions ◽

10.1042/bst20190124 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1247-1257 ◽

Cited By ~ 17

Author(s):

Mateusz Dyla ◽

Sara Basse Hansen ◽

Poul Nissen ◽

Magnus Kjaergaard

Keyword(s):

Structural Dynamics ◽

Single Molecule ◽

New Technologies ◽

Atp Hydrolysis ◽

Resonance Energy Transfer ◽

Resonance Energy ◽

Time Resolved ◽

Dynamics Simulations ◽

Types Of Information ◽

P Type

Abstract P-type ATPases transport ions across biological membranes against concentration gradients and are essential for all cells. They use the energy from ATP hydrolysis to propel large intramolecular movements, which drive vectorial transport of ions. Tight coordination of the motions of the pump is required to couple the two spatially distant processes of ion binding and ATP hydrolysis. Here, we review our current understanding of the structural dynamics of P-type ATPases, focusing primarily on Ca2+ pumps. We integrate different types of information that report on structural dynamics, primarily time-resolved fluorescence experiments including single-molecule Förster resonance energy transfer and molecular dynamics simulations, and interpret them in the framework provided by the numerous crystal structures of sarco/endoplasmic reticulum Ca2+-ATPase. We discuss the challenges in characterizing the dynamics of membrane pumps, and the likely impact of new technologies on the field.

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