Protein Misfolding Disorders: A Trip into the ER

The Unfolded Protein Response in Mammalian Cells

Author(s): Sung Hoon Back, Justin R. Hassler and Randal J. Kaufman

Pp: 19-46 (28)

DOI: 10.2174/978160805013010901010019

* (Excluding Mailing and Handling)

Abstract

The endoplasmic reticulum (ER) is a well-orchestrated factory where secretory and membrane proteins are manufactured, modified and correctly folded prior to trafficking to their final destinations. Conditions that interfere with ER function lead to an evolutionarily conserved cellular stress response termed the unfolded protein response (UPR). The UPR initially transduces signals to reestablish ER homeostasis but with prolonged or acute ER stress these signals undergo a transition that initiate cell death. In this review, we summarize our current understanding of the mammalian UPR and discuss the cell-type and tissue-specific functions of UPR components revealed by studies from genetic mouse models.

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      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
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      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
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      • 16. app/Models/Subject.php:238
      • 17. app/Http/Controllers/ChapterController.php:1434
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 19. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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      • 14. app/Models/Subject.php:238
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      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
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      510μsalphaeurekaselec_live_10_06_2022Subject.php#255
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      • 16. app/Models/Subject.php:255
      • 17. app/Http/Controllers/ChapterController.php:1435
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
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      520μsalphaeurekaselec_live_10_06_2022Subject.php#255
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      • 15. app/Http/Controllers/ChapterController.php:1435
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
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      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
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      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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      400μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1465
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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      900μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1478
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314340157 and j.to_ip >=314340157 )) and ((j.from_date <= 1740473376 and j.to_date >= 1740473376 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2681) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314340157 and j.to_ip >=314340157 )) and ((j.from_date <= 1740473376 and j.to_date >= 1740473376 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2681) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314340157 and j.to_ip >=314340157 )) and ((j.from_date <= 1740473376 and j.to_date >= 1740473376 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2681)
      930μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 972 and `b`.`banner_from_date` <= 1740473376 and `b`.`banner_to_date` >= 1740473376 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.47msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 972
      • 3: 1740473376
      • 4: 1740473376
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='bb44acdc8aa7b1860e65a88e94ac79a9'
      220μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Keywords
    1Keywords.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        agc7VRO3uRTRi5pNQL31vPnT7ajfM4hWvEnCfM1S
        uc_cart_id
        bb44acdc8aa7b1860e65a88e94ac79a9
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/chapter/2681" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/2681
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 08:49:36 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjR4Znh3K0pMUFpwZzdWUHF4ei83SGc9PSIsInZhbHVlIjoia1Z1Q2xBeGlmaTFFUlkvamppaDJ5dUJSczQ5WjBwWDFkb3NRRm9KakFTdVFocDFscktKc2RZc3FKNVF4aEtPWXB2Sjh3bXZsQWFLTzhuQ3lJR3Q5Q0ZyOEs0MmpEc1FEYlpYY1NNeHBjV0c3dmFkSkRaRUpvRVhVNHRYaXV5b1MiLCJtYWMiOiJhYTllODA3NDJmZTEwNjQ1N2QzOTZkMDMyOWY4ZGYzZjdiZTQ3YWQ0OGY3ZDUyNTc4ODVhMTg1Yzk1Yjk5MDExIiwidGFnIjoiIn0%3D; expires=Thu, 27 Feb 2025 20:49:36 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IjR4Znh3K0pMUFpwZzdWUHF4ei83SGc9PSIsInZhbHVlIjoia1Z1Q2xBeGlmaTFFUlkvamppaDJ5dUJSczQ5WjBwWDFkb3NRRm9KakFTdVFocDFscktKc2RZc3FKNVF4aEtPWXB2Sjh3b" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkFuTWlkT01qK0NLRWpjMXFRNzZMVWc9PSIsInZhbHVlIjoiQit0TytESTBtN0tlVG1FYmV6UFd4K0FDU2FrV0tQaVNQV0J2YkZoSTVqK1k0dXNsY0FDUmRCT1czODlQYVQwNUN5V3dVSVV4a1Q0Y1JqQjZheWNsQVN5NzZuSUxDL1MvNFlMcFJnKzhqWkovNjRXL2pZWjk1V0NtQjE3UHN4aEwiLCJtYWMiOiIxNDI1Njc3NjY3MDk1YmM1OTIyZDQ4ZjE4MTJhM2EzZTQ0NTJkNGNiODhlNzgzODdjNTRhYzU4NDI1OGZhNmUyIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IkFuTWlkT01qK0NLRWpjMXFRNzZMVWc9PSIsInZhbHVlIjoiQit0TytESTBtN0tlVG1FYmV6UFd4K0FDU2FrV0tQaVNQV0J2YkZoSTVqK1k0dXNsY0FDUmRCT1c" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjR4Znh3K0pMUFpwZzdWUHF4ei83SGc9PSIsInZhbHVlIjoia1Z1Q2xBeGlmaTFFUlkvamppaDJ5dUJSczQ5WjBwWDFkb3NRRm9KakFTdVFocDFscktKc2RZc3FKNVF4aEtPWXB2Sjh3bXZsQWFLTzhuQ3lJR3Q5Q0ZyOEs0MmpEc1FEYlpYY1NNeHBjV0c3dmFkSkRaRUpvRVhVNHRYaXV5b1MiLCJtYWMiOiJhYTllODA3NDJmZTEwNjQ1N2QzOTZkMDMyOWY4ZGYzZjdiZTQ3YWQ0OGY3ZDUyNTc4ODVhMTg1Yzk1Yjk5MDExIiwidGFnIjoiIn0%3D; expires=Thu, 27-Feb-2025 20:49:36 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IjR4Znh3K0pMUFpwZzdWUHF4ei83SGc9PSIsInZhbHVlIjoia1Z1Q2xBeGlmaTFFUlkvamppaDJ5dUJSczQ5WjBwWDFkb3NRRm9KakFTdVFocDFscktKc2RZc3FKNVF4aEtPWXB2Sjh3b" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkFuTWlkT01qK0NLRWpjMXFRNzZMVWc9PSIsInZhbHVlIjoiQit0TytESTBtN0tlVG1FYmV6UFd4K0FDU2FrV0tQaVNQV0J2YkZoSTVqK1k0dXNsY0FDUmRCT1czODlQYVQwNUN5V3dVSVV4a1Q0Y1JqQjZheWNsQVN5NzZuSUxDL1MvNFlMcFJnKzhqWkovNjRXL2pZWjk1V0NtQjE3UHN4aEwiLCJtYWMiOiIxNDI1Njc3NjY3MDk1YmM1OTIyZDQ4ZjE4MTJhM2EzZTQ0NTJkNGNiODhlNzgzODdjNTRhYzU4NDI1OGZhNmUyIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IkFuTWlkT01qK0NLRWpjMXFRNzZMVWc9PSIsInZhbHVlIjoiQit0TytESTBtN0tlVG1FYmV6UFd4K0FDU2FrV0tQaVNQV0J2YkZoSTVqK1k0dXNsY0FDUmRCT1c" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "agc7VRO3uRTRi5pNQL31vPnT7ajfM4hWvEnCfM1S" "uc_cart_id" => "bb44acdc8aa7b1860e65a88e94ac79a9" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/chapter/2681" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 08:49:36GET/chapter/2681112193