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ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function.

ABSTRACT: Derlin family members (Derlins) are primarily known as components of the endoplasmic reticulum-associated degradation pathway that eliminates misfolded proteins. Here we report a function of Derlins in the brain development. Deletion of Derlin-1 or Derlin-2 in the central nervous system of mice impaired postnatal brain development, particularly of the cerebellum and striatum, and induced motor control deficits. Derlin-1 or Derlin-2 deficiency reduced neurite outgrowth in vitro and in vivo and surprisingly also inhibited sterol regulatory element binding protein 2 (SREBP-2)-mediated brain cholesterol biosynthesis. In addition, reduced neurite outgrowth due to Derlin-1 deficiency was rescued by SREBP-2 pathway activation. Overall, our findings demonstrate that Derlins sustain brain cholesterol biosynthesis, which is essential for appropriate postnatal brain development and function.

SUBMITTER: Sugiyama T

PROVIDER: S-EPMC8324814 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function.

Sugiyama Takashi T Murao Naoya N Kadowaki Hisae H Takao Keizo K Miyakawa Tsuyoshi T Matsushita Yosuke Y Katagiri Toyomasa T Futatsugi Akira A Shinmyo Yohei Y Kawasaki Hiroshi H Sakai Juro J Shiomi Kazutaka K Nakazato Masamitsu M Takeda Kohsuke K Mikoshiba Katsuhiko K Ploegh Hidde L HL Ichijo Hidenori H Nishitoh Hideki H

iScience 20210619 7

Derlin family members (Derlins) are primarily known as components of the endoplasmic reticulum-associated degradation pathway that eliminates misfolded proteins. Here we report a function of Derlins in the brain development. Deletion of Derlin-1 or Derlin-2 in the central nervous system of mice impaired postnatal brain development, particularly of the cerebellum and striatum, and induced motor control deficits. Derlin-1 or Derlin-2 deficiency reduced neurite outgrowth in vitro</ ...[more]

PMID: 34355142

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Project description:BackgroundPostnatal Care (PNC) is one of the healthcare-packages in the continuum of care for mothers and children that needs to be in place to reduce global maternal and perinatal mortality and morbidity. We sought to identify the essential components of PNC and develop signal functions to reflect these which can be used for the monitoring and evaluation of availability and quality of PNC.MethodsSystematic review of the literature using MESH headings for databases (Cinahl, Cochrane, Global Health, Medline, PubMed, and Web of Science). Papers and reports on content of PNC published from 2000-2020 were included. Narrative synthesis of data and development of signal function through 7 consensus-building workshops with 184 stakeholders.ResultsForty-Eight papers and reports are included in the systematic review from which 22 essential components of PNC were extracted and used to develop 14 signal functions. Signal functions are used in obstetrics to denote a list of interventions that address major causes of maternal and perinatal morbidity or mortality. For each signal function we identified the equipment, medication and consumables required for implementation. The prevention and management of infectious diseases (malaria, HIV, tuberculosis) are considered essential components of routine PNC depending on population disease burden or whether the population is considered at risk. Screening and management of pre-eclampsia, maternal anaemia and mental health are recommended universally. Promotion of and support of exclusive breastfeeding and uptake of a modern contraceptive method are also considered essential components of PNC. For the new-born baby, cord care, monitoring of growth and development, screening for congenital disease and commencing vaccinations are considered essential signal functions. Screening for gender-based violence (GBV) including intimate partner- violence (IPV) is recommended when counselling can be provided and/or a referral pathway is in place. Debriefing following birth (complicated or un-complicated) was agreed through consensus-building as an important component of PNC.ConclusionsSignal functions were developed which can be used for monitoring and evaluation of content and quality of PNC. Country adaptation and validation is recommended and further work is needed to examine if the proposed signal functions can serve as a useful monitoring and evaluation tool.Trial registrationThe systematic review protocol was registered: PROSPERO 2018 CRD42018107054 .

Dataset Information

ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function.

Publications

ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function.

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