PMID- 35095425
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220201
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 15
DP  - 2021
TI  - Neuroprogenitor Cells From Patients With TBCK Encephalopathy Suggest Deregulation 
      of Early Secretory Vesicle Transport.
PG  - 803302
LID - 10.3389/fncel.2021.803302 [doi]
LID - 803302
AB  - Biallelic pathogenic variants in TBCK cause encephaloneuropathy, infantile 
      hypotonia with psychomotor retardation, and characteristic facies 3 (IHPRF3). The 
      molecular mechanisms underlying its neuronal phenotype are largely unexplored. In 
      this study, we reported two sisters, who harbored biallelic variants in TBCK and 
      met diagnostic criteria for IHPRF3. We provided evidence that TBCK may play an 
      important role in the early secretory pathway in neuroprogenitor cells (iNPC) 
      differentiated from induced pluripotent stem cells (iPSC). Lack of functional 
      TBCK protein in iNPC is associated with impaired endoplasmic reticulum-to-Golgi 
      vesicle transport and autophagosome biogenesis, as well as altered cell cycle 
      progression and severe impairment in the capacity of migration. Alteration in 
      these processes, which are crucial for neurogenesis, neuronal migration, and 
      cytoarchitecture organization, may represent an important causative mechanism of 
      both neurodevelopmental and neurodegenerative phenotypes observed in IHPRF3. 
      Whether reduced mechanistic target of rapamycin (mTOR) signaling is secondary to 
      impaired TBCK function over other secretory transport regulators still needs 
      further investigation.
CI  - Copyright (c) 2022 Moreira, Suzuki, Silva, Varella-Branco, Meneghetti, Kobayashi, 
      Fogo, Ferrari, Cardoso, Lourenco, Griesi-Oliveira, Zachi, Bertola, Weinmann, 
      Lima, Nader, Sertie and Passos-Bueno.
FAU - Moreira, Danielle de Paula
AU  - Moreira DP
AD  - Centro de Pesquisas Sobre o Genoma Humano e Celulas-Tronco, Instituto de 
      Biociencias, Universidade de Sao Paulo, Sao Paulo, Brazil.
FAU - Suzuki, Angela May
AU  - Suzuki AM
AD  - Centro de Pesquisas Sobre o Genoma Humano e Celulas-Tronco, Instituto de 
      Biociencias, Universidade de Sao Paulo, Sao Paulo, Brazil.
FAU - Silva, Andre Luiz Teles E
AU  - Silva ALTE
AD  - Instituto de Ensino e Pesquisa Albert Einstein, Albert Einstein Hospital, Sao 
      Paulo, Brazil.
FAU - Varella-Branco, Elisa
AU  - Varella-Branco E
AD  - Centro de Pesquisas Sobre o Genoma Humano e Celulas-Tronco, Instituto de 
      Biociencias, Universidade de Sao Paulo, Sao Paulo, Brazil.
FAU - Meneghetti, Maria Cecilia Zorel
AU  - Meneghetti MCZ
AD  - Departamento de Bioquimica, Escola Paulista de Medicina, Universidade Federal de 
      Sao Paulo, Sao Paulo, Brazil.
FAU - Kobayashi, Gerson Shigeru
AU  - Kobayashi GS
AD  - Centro de Pesquisas Sobre o Genoma Humano e Celulas-Tronco, Instituto de 
      Biociencias, Universidade de Sao Paulo, Sao Paulo, Brazil.
FAU - Fogo, Mariana
AU  - Fogo M
AD  - Centro de Pesquisas Sobre o Genoma Humano e Celulas-Tronco, Instituto de 
      Biociencias, Universidade de Sao Paulo, Sao Paulo, Brazil.
AD  - Instituto de Ensino e Pesquisa Albert Einstein, Albert Einstein Hospital, Sao 
      Paulo, Brazil.
FAU - Ferrari, Merari de Fatima Ramires
AU  - Ferrari MFR
AD  - Departamento de Genetica e Biologia Evolutiva, Instituto de Biociencias, 
      Universidade de Sao Paulo, Sao Paulo, Brazil.
FAU - Cardoso, Rafaela Regina
AU  - Cardoso RR
AD  - Departamento de Genetica e Biologia Evolutiva, Instituto de Biociencias, 
      Universidade de Sao Paulo, Sao Paulo, Brazil.
FAU - Lourenco, Naila Cristina Vilaca
AU  - Lourenco NCV
AD  - Centro de Pesquisas Sobre o Genoma Humano e Celulas-Tronco, Instituto de 
      Biociencias, Universidade de Sao Paulo, Sao Paulo, Brazil.
FAU - Griesi-Oliveira, Karina
AU  - Griesi-Oliveira K
AD  - Centro de Pesquisas Sobre o Genoma Humano e Celulas-Tronco, Instituto de 
      Biociencias, Universidade de Sao Paulo, Sao Paulo, Brazil.
AD  - Instituto de Ensino e Pesquisa Albert Einstein, Albert Einstein Hospital, Sao 
      Paulo, Brazil.
FAU - Zachi, Elaine Cristina
AU  - Zachi EC
AD  - Centro de Pesquisas Sobre o Genoma Humano e Celulas-Tronco, Instituto de 
      Biociencias, Universidade de Sao Paulo, Sao Paulo, Brazil.
FAU - Bertola, Debora Romeo
AU  - Bertola DR
AD  - Centro de Pesquisas Sobre o Genoma Humano e Celulas-Tronco, Instituto de 
      Biociencias, Universidade de Sao Paulo, Sao Paulo, Brazil.
AD  - Instituto da Crianca do Hospital das Clinicas, Faculdade de Medicina da 
      Universidade de Sao Paulo, Sao Paulo, Brazil.
FAU - Weinmann, Karina de Souza
AU  - Weinmann KS
AD  - Centro de Pesquisas Sobre o Genoma Humano e Celulas-Tronco, Instituto de 
      Biociencias, Universidade de Sao Paulo, Sao Paulo, Brazil.
FAU - de Lima, Marcelo Andrade
AU  - de Lima MA
AD  - Departamento de Bioquimica, Escola Paulista de Medicina, Universidade Federal de 
      Sao Paulo, Sao Paulo, Brazil.
FAU - Nader, Helena Bonciani
AU  - Nader HB
AD  - Departamento de Bioquimica, Escola Paulista de Medicina, Universidade Federal de 
      Sao Paulo, Sao Paulo, Brazil.
FAU - Sertie, Andrea Laurato
AU  - Sertie AL
AD  - Instituto de Ensino e Pesquisa Albert Einstein, Albert Einstein Hospital, Sao 
      Paulo, Brazil.
FAU - Passos-Bueno, Maria Rita
AU  - Passos-Bueno MR
AD  - Centro de Pesquisas Sobre o Genoma Humano e Celulas-Tronco, Instituto de 
      Biociencias, Universidade de Sao Paulo, Sao Paulo, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20220113
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC8793280
OTO - NOTNLM
OT  - GM130
OT  - STAM
OT  - autophagy
OT  - clathrin
OT  - early secretory pathway
OT  - iPSC-neurodevelopmental disease modeling
OT  - mTOR
OT  - vesicle trafficking
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/02/01 06:00
MHDA- 2022/02/01 06:01
PMCR- 2021/01/01
CRDT- 2022/01/31 05:55
PHST- 2021/10/27 00:00 [received]
PHST- 2021/12/15 00:00 [accepted]
PHST- 2022/01/31 05:55 [entrez]
PHST- 2022/02/01 06:00 [pubmed]
PHST- 2022/02/01 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2021.803302 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2022 Jan 13;15:803302. doi: 10.3389/fncel.2021.803302. 
      eCollection 2021.