GPI Membrane Anchors – The Much Needed link

GPI-Anchored Proteins and Their Cellular Surroundings: Signalling, Function and Medical Implications of Membrane Microdomains

Author(s): Vera Michel, David W.L. Ma and Marica Bakovic

Pp: 1-18 (18)

DOI: 10.2174/978160805123611001010001

* (Excluding Mailing and Handling)

Abstract

Sphingolipid- and cholesterol-rich membrane microdomains, often referred to as lipid rafts, harbour various plasma membrane proteins and can putatively provide a specific signalling platform for these proteins. Rafts were originally discovered as detergent-resistant lipid domains, but widely differing methods of isolation and analysis have led to numerous classifications, and there is still no coherence which further complicates the study of these domains. Subclasses of lipid rafts have been categorized depending on the specific lipid- and protein-composition, such as caveolae, raft-domains rich in caveolin proteins with tissue-specific signalling properties. Some lipid raft proteins are post-translationally modified by the covalent attachment of a glycosylphosphatidylinositol (GPI) anchor. The complexity of the GPI anchor implies a function beyond directing proteins to the plasma membrane, such as cell-cell communication, regulation of protein structure and cleavage, signal transduction and protein targeting. The mechanisms by which GPI-anchored outer membrane proteins may initiate intracellular signalling events are largely unknown; however several protein kinases have been implicated.

The importance of lipid microdomains becomes apparent in the raft localization of numerous proteins involved in the pathogenesis of diseases. These include neurological diseases such as Alzheimer’s and prion diseases, immunological diseases such as lupus erythematosus, and cardiovascular disease. Interestingly, the lipid composition of lipid rafts can be altered nutritionally, especially through dietary long chain fatty acids, which could potentially make lipid rafts an attractive pharmacological target.

Here we will analyze the signalling properties of lipid raft proteins and discuss their importance in health and disease.

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      • 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 <= 59755419 and j.to_ip >=59755419 )) and ((j.from_date <= 1739847679 and j.to_date >= 1739847679 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1855) 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 <= 59755419 and j.to_ip >=59755419 )) and ((j.from_date <= 1739847679 and j.to_date >= 1739847679 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1855) 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 <= 59755419 and j.to_ip >=59755419 )) and ((j.from_date <= 1739847679 and j.to_date >= 1739847679 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1855)
      530μsalphaeurekaselec_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` = 922 and `b`.`banner_from_date` <= 1739847679 and `b`.`banner_to_date` >= 1739847679 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.07msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 922
      • 3: 1739847679
      • 4: 1739847679
      • 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='625900dcbc907895da4da1a268bb6697'
      210μsalphaeurekaselec_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
        Ubm4aerU9SREcmfVPToC9VYlULryExRclwo6XjBK
        uc_cart_id
        625900dcbc907895da4da1a268bb6697
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/1855" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/1855
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
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        request_cookies
        0 of 0
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        response_headers
        0 of 0
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-18 03:01:19GET/chapter/1855112193