Keyword search (3,619 papers available)


The phenotype associated with variants in TANGO2 may be explained by a dual role of the protein in ER-to-Golgi transport and at the mitochondria.

Author(s): Milev MP, Saint-Dic D, Zardoui K, Klopstock T, Law C, Distelmaier F, Sacher M

TANGO2 variants result in a complex disease phenotype consisting of recurrent crisis-induced rhabdomyolysis, encephalopathy, seizures, lactic acidosis, hypoglycemia, and cardiac arrhythmias. Although first described in a fruit fly model as a protein necessa...

Article GUID: 32909282
A novel homozygous variant in TRAPPC2L results in a neurodevelopmental disorder and disrupts TRAPP complex function.

Author(s): Al-Deri N, Okur V, Ahimaz P, Milev M, Valivullah Z, Hagen J, Sheng Y, Chung W, Sacher M, Ganapathi M...

BACKGROUND: Next-generation sequencing has facilitated the diagnosis of neurodevelopmental disorders with variable and non-specific clinical findings. Recently, a homozygous missense p.(Asp37Tyr) v...

Article GUID: 32843486
TRAPPing a neurological disorder: from yeast to humans.

Author(s): Lipatova Z, Van Bergen N, Stanga D, Sacher M, Christodoulou J, Segev N

Autophagy. 2020 Mar 02;: Authors: Lipatova Z, Van Bergen N, Stanga D, Sacher M, Christodoulou J, Segev N

Article GUID: 32116085
Deficiencies in vesicular transport mediated by TRAPPC4 are associated with severe syndromic intellectual disability.

Author(s): Van Bergen NJ, Guo Y, Al-Deri N, Lipatova Z, Stanga D, Zhao S, Murtazina R, Gyurkovska V, Pehlivan D, Mitani T, Gezdirici A, Antony J, Colli...

The conserved transport protein particle (TRAPP) complexes regulate key trafficking events and are required for autophagy. TRAPPC4, like its yeast Trs23 orthologue, is a core component of the TRAPP...

Article GUID: 31794024
Characterization of three TRAPPC11 variants suggests a critical role for the extreme carboxy terminus of the protein.

Author(s): Milev MP, Stanga D, Schänzer A, Nascimento A, Saint-Dic D, Ortez C, Benito DN, Barrios DG, Colomer J, Badosa C, Jou C, Gallano P, Gonzalez-Q...

Sci Rep. 2019 Oct 01;9(1):14036 Authors: Milev MP, Stanga D, Schänzer A, Nascimento A, Saint-Dic D, Ortez C, Benito DN, Barrios DG, Colomer J, Badosa C, Jou C, Gallano P, Gonzalez-Quereda L, ...

Article GUID: 31575891
Mutations in TRAPPC12 Manifest in Progressive Childhood Encephalopathy and Golgi Dysfunction.

Author(s): Milev MP, Grout ME, Saint-Dic D, Cheng YH, Glass IA, Hale CJ, Hanna DS, Dorschner MO, Prematilake K, Shaag A, Elpeleg O, Sacher M, Doherty D...

Am J Hum Genet. 2017 Aug 03;101(2):291-299 Authors: Milev MP, Grout ME, Saint-Dic D, Cheng YH, Glass IA, Hale CJ, Hanna DS, Dorschner MO, Prematilake K, Shaag A, Elpeleg O, Sacher M, Doherty D, Ed...

Article GUID: 28777934
TRAMM/TrappC12 plays a role in chromosome congression, kinetochore stability, and CENP-E recruitment.

Author(s): Milev MP, Hasaj B, Saint-Dic D, Snounou S, Zhao Q, Sacher M

J Cell Biol. 2015 Apr 27;209(2):221-34 Authors: Milev MP, Hasaj B, Saint-Dic D, Snounou S, Zhao Q, Sacher M

Article GUID: 25918224
TRAPPC11 and GOSR2 mutations associate with hypoglycosylation of α-dystroglycan and muscular dystrophy.

Author(s): Larson AA, Baker PR, Milev MP, Press CA, Sokol RJ, Cox MO, Lekostaj JK, Stence AA, Bossler AD, Mueller JM, Prematilake K, Tadjo TF, Williams...

Skelet Muscle. 2018 05 31;8(1):17 Authors: Larson AA, Baker PR, Milev MP, Press CA, Sokol RJ, Cox MO, Lekostaj JK, Stence AA, Bossler AD, Mueller JM, Prematilake K, Tadjo TF, Williams CA, Sacher M...

Article GUID: 29855340
Bi-allelic mutations in TRAPPC2L result in a neurodevelopmental disorder and have an impact on RAB11 in fibroblasts.

Author(s): Milev MP, Graziano C, Karall D, Kuper WFE, Al-Deri N, Cordelli DM, Haack TB, Danhauser K, Iuso A, Palombo F, Pippucci T, Prokisch H, Saint-D...

J Med Genet. 2018 Nov;55(11):753-764 Authors: Milev MP, Graziano C, Karall D, Kuper WFE, Al-Deri N, Cordelli DM, Haack TB, Danhauser K, Iuso A, Palombo F, Pippucci T, Prokisch H, Saint-Dic D, Seri...

Article GUID: 30120216
TRAPPopathies: An emerging set of disorders linked to variations in the genes encoding transport protein particle (TRAPP)-associated proteins.

Author(s): Sacher M, Shahrzad N, Kamel H, Milev MP

Traffic. 2019 01;20(1):5-26 Authors: Sacher M, Shahrzad N, Kamel H, Milev MP

Article GUID: 30152084
TRAPPC11 functions in autophagy by recruiting ATG2B-WIPI4/WDR45 to preautophagosomal membranes.

Author(s): Stanga D, Zhao Q, Milev MP, Saint-Dic D, Jimenez-Mallebrera C, Sacher M

Traffic. 2019 May;20(5):325-345 Authors: Stanga D, Zhao Q, Milev MP, Saint-Dic D, Jimenez-Mallebrera C, Sacher M

Article GUID: 30843302
Title:TRAPPing a neurological disorder: from yeast to humans.
Authors:Lipatova Z,  Van Bergen N,  Stanga D,  Sacher M,  Christodoulou J,  Segev N
Link:https://www.ncbi.nlm.nih.gov/pubmed/32116085?dopt=Abstract
DOI:10.1080/15548627.2020.1736873
Category:Autophagy
PMID:32116085
Dept Affiliation: BIOLOGY
1 Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
2 Brain and Mitochondrial Research Group, Murdoch Children's Research Institute, Royal Children's Hospital, and Department of Pediatrics, University of Melbourne, Melbourne, Australia.
3 Department of Biology, Concordia University, Montreal, Canada.

Description:

TRAPPing a neurological disorder: from yeast to humans.

Autophagy. 2020 Mar 02;:

Authors: Lipatova Z, Van Bergen N, Stanga D, Sacher M, Christodoulou J, Segev N

Abstract

The modular complex TRAPP acts as an activator of a subgroup of Ypt/RAB GTPases. The substrate GTPases and TRAPP are conserved from yeast to human cells, required for secretion and macroautophagy/autophagy and implicated in human disease. All TRAPP complexes contain four core subunits essential for cell viability, and until recently there were no human diseases associated with any core TRAPP subunit. Recently, we reported a neurological disorder associated with a pathogenic variant of the core TRAPP subunit TRAPPC4. This variant results in lower levels of full-length TRAPPC4 protein and the TRAPP complex. A conditional mutation of the yeast homolog of TRAPPC4, Trs23, also results in a lower level of the protein and the TRAPP complex. Phenotypic analysis of the yeast mutant cells reveals a minor defect in secretion and a major defect in autophagy. Similarly, primary fibroblasts derived from human patients also exhibit minor and severe defects in secretion and autophagy, respectively. We propose that the autophagy defect caused by the pathogenic-TRAPPC4 variant results in the severe neurological disorder. Moreover, we hypothesize that low levels of the core TRAPP complex are more detrimental to autophagy than to secretion, and that the long-term autophagy defect is especially harmful to neuronal cells.

PMID: 32116085 [PubMed - as supplied by publisher]