SPTSSA variants alter sphingolipid synthesis and cause a complex hereditary spastic paraplegia
Abstract
Sphingolipids are a diverse family of lipids with critical structural and signalling functions in the mammalian nervous system, where they are abundant in myelin membranes. Serine palmitoyltransferase, the enzyme that catalyses the rate-limiting reaction of sphingolipid synthesis, is composed of multiple subunits including an activating subunit, SPTSSA. Sphingolipids are both essential and cytotoxic and their synthesis must therefore be tightly regulated. Key to the homeostatic regulation are the ORMDL proteins that are bound to serine palmitoyltransferase and mediate feedback inhibition of enzymatic activity when sphingolipid levels become excessive.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 30, 2023
- Source ID
- 10.1093/brain/awac460
Entities
People
- Aaron Quinlan
- Adeline Vanderver
- Alan H. Beggs
- Alana Grajewski
- Alden Huang
- Alexa T Mccray
- Alica M Goldman
- Allyn Mcconkie-rosell
- Alyssa A Tran
- Amy K Robertson
- Andrew B Crouse
- Angela Sun
- Anita Beck
- Anna Bican
- Anna Nagy
- Anne Hing
- Archana N Raja
- Argenia L Doss
- Ashley Andrews
- Ashok Balasubramanyam
- Audrey Thurm
- Avi Nath
- Barbara N Pusey
- Ben Solomon
- Benjamin P Kleinstiver
- Bernadette Gochuico
- Beth A Martin
- Beverly Berg-rood
- Bradley Power
- Brendan C Lanpher
- Brendan Lee
- Brenna Boyd
- Brent L Fogel
- Brian Wishart
- Brianna M Tucker
- Bryan C Mak
- Byron Lam
- C Ron Scott
- Calum A. Macrae
- Camilo Toro
- Carlos A Bacino
- Carlos Ferreira
- Carsten Bonnenmann
- Catherine A Groden
- Cecilia Esteves
- Chia-Hsueh Lee
- Chloe M Reuter
- Chris A Walsh
- Christina G S Palmer
- Christina Lam
- Christine M Eng
- Chunli Zhao
- Claudia Brito Pires
- Colleen E Mccormack
- Colleen E Wahl
- Cynthia J Tifft
- Cynthia M Cooper
- Dana Kiley
- Daniel Doherty
- Daniel Wegner
- Daryl A Scott
- Dave Viskochi
- David A Sweetser
- David B. Goldstein
- David D Draper
- David J Eckstein
- David R Adams
- David R Murdock
- Dawn Earl
- Deborah Barbouth
- Deborah Krakow
- Deborah Mosbrook-davis
- Deborah Nickerson
- Deepak A Rao
- Devin Oglesbee
- Devon Bonner
- Diane B Zastrow
- Donna M Krasnewich
- Donna Novacic
- Dustin Baldridge
- Edward Behrens
- Edward C Smith
- Edwin K. Silverman
- Elijah Kravets
- Elisabeth Mcgee
- Elizabeth A Burke
- Elizabeth Blue
- Elizabeth Doney
- Elizabeth L Fieg
- Ellen F Macnamara
- Elly Brokamp
- Emilie D. Douine
- Emily G Kelley
- Emily Solem
- Esteban C Dell’angelica
- Euan A. Ashley
- Eva Baker
- Eva Morava
- F. Sessions Cole
- Fariha Jamal
- Florian S Eichler
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- Gabor Marth
- Gabrielle Brown
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- Gary D Clark
- Genecee Renteria
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- Ghayda Mirzaa
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- Guney Bademci
- Hagar Mor Shaked
- Hane Lee
- Hannah Stutzman
- Heather A Colley
- Heather Mefford
- Heidi Cope
- Holly K Tabor
- Hongzheng Dai
- Hsiao-tuan Chao
- Hugo J. Bellen
- Ian Glass
- Ian R Lanza
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- Irma Gutierrez
- Irman Forghani
- Isaac S. Kohane
- J Carl Pallais
- J Lawrence Merritt
- Jacinda B. Sampson
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- Janet S Sinsheimer
- Jason Hom
- Jeanette C Papp
- Jeffrey Jarvik
- Jennefer N Kohler
- Jennifer A Sullivan
- Jennifer E. Posey
- Jennifer Kennedy
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- Joel B. Krier
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- Jonathan A Bernstein
- Jordan Whitlock
- Joseph Loscalzo
- Joy D Cogan
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- Julian A. Martinez-agosto
- Justin Alvey
- Jyoti G Dayal
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- Lee-kai Wang
- Lefkothea Karaviti
- Liliana Fernandez
- Lilianna Solnica-krezel
- Lindsay C Burrage
- Lisa T. Emrick
- Lorenzo Botto
- Lorraine Potocki
- Lynette Rives
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- Madison P Goldrich
- Mahshid S Azamian
- Manish J. Butte
- Marc Gotkine
- Margaret Adam
- Maria T. Acosta
- Mariko Nakano-okuno
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- Melissa Walker
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- Michael Bamshad
- Michael Cunningham
- Michael F Wangler
- Monte Westerfield
- Muhammad Yousef
- Mustafa Tekin
- Naghmeh Dorrani
- Natalie Rosenwasser
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- Niranjanakumari Somashekarappa
- Olveen Carrasquillo
- Orly Elpeleg
- Pankaj B Agrawal
- Paolo M Moretti
- Paolo Moretti
- Patricia A Ward
- Paul G. Fisher
- Paula Goldenberg
- Payam Mohassel
- Pengfei Liu
- Peter Byers
- Pinar Bayrak-toydemir
- Precilla D’souza
- Queenie K G Tan
- Queenie K-g Tan
- Ralph Sacco
- Rebecca C Spillmann
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- Rena A Godfrey
- Reza Sadjadi
- Richard A Lewis
- Richard L Maas
- Rizwan Hamid
- Rong Mao
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- Sarah K Nicholas
- Scott Smith
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- Sharyn A Lincoln
- Shinya Yamamoto
- Shirley Nieves-rodriguez
- Shirley Sutton
- Shruti Marwaha
- Shweta U Dhar
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- Stanley F. Nelson
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- Yong Huang
Organizations
- Baylor College of Medicine
- Congressionally Directed Medical Research Programs
- Division of Program Coordination Planning and Strategic Initiatives
- Duke University
- Hadassah Medical Center
- Harvard Medical School
- Hebrew University of Jerusalem
- Margaret Q. Landenberger Research Foundation
- Massachusetts Eye and Ear Infirmary
- Massachusetts General Hospital
- National Institute of Neurological Disorders and Stroke
- Office of the Director
- St. Jude Children's Research Hospital
- Texas Children's Hospital
- Uniformed Services University of the Health Sciences