{"id":65321,"date":"2023-03-09T12:29:43","date_gmt":"2023-03-09T11:29:43","guid":{"rendered":"https:\/\/cri1149.fr\/?post_type=publications&#038;p=65321"},"modified":"2025-09-11T16:47:57","modified_gmt":"2025-09-11T14:47:57","slug":"rab44-regulates-murine-mast-cell-driven-anaphylaxis-through-kinesin-1-dependent-secretory-granule-translocation","status":"publish","type":"publication","link":"https:\/\/cri1149.fr\/en\/publication\/rab44-regulates-murine-mast-cell-driven-anaphylaxis-through-kinesin-1-dependent-secretory-granule-translocation\/","title":{"rendered":"Rab44 regulates murine mast cell-driven anaphylaxis through kinesin-1-dependent secretory granule translocation"},"content":{"rendered":"","protected":false},"featured_media":0,"template":"","meta":{"_acf_changed":false,"_EventAllDay":false,"_EventTimezone":"","_EventStartDate":"","_EventEndDate":"","_EventStartDateUTC":"","_EventEndDateUTC":"","_EventShowMap":false,"_EventShowMapLink":false,"_EventURL":"","_EventCost":"","_EventCostDescription":"","_EventCurrencySymbol":"","_EventCurrencyCode":"","_EventCurrencyPosition":"","_EventDateTimeSeparator":"","_EventTimeRangeSeparator":"","_EventOrganizerID":[],"_EventVenueID":[],"_OrganizerEmail":"","_OrganizerPhone":"","_OrganizerWebsite":"","_VenueAddress":"","_VenueCity":"","_VenueCountry":"","_VenueProvince":"","_VenueState":"","_VenueZip":"","_VenuePhone":"","_VenueURL":"","_VenueStateProvince":"","_VenueLat":"","_VenueLng":"","_VenueShowMap":false,"_VenueShowMapLink":false},"category_publication":[],"class_list":["post-65321","publication","type-publication","status-publish","hentry"],"acf":{"numero_de_publication":"J Allergy Clin Immunol.","date_de_publication":"20220901","numero_doi":"","equipe":[101],"auteurs-liste":[{"texte_libre":true,"auteur-lien":null,"auteur-text":"Cyril Long\u00e9"},{"texte_libre":false,"auteur-lien":13190,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Mathieu Kurowska"},{"texte_libre":false,"auteur-lien":13185,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Pierre David"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Val\u00e8re Desmeure"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Jian-Dong Huang"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Alain Fischer"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Genevi\u00e8ve de Saint Basile"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Fernando E Sepulveda"},{"texte_libre":false,"auteur-lien":13037,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Ga\u00ebl M\u00e9nasch\u00e9"}],"auteurs-manuel":"","liens_externes":null,"liens":[{"lien":"https:\/\/pubmed.ncbi.nlm.nih.gov\/35469841\/"}],"paragraphe":"<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Background:\u00a0<\/strong>Mast cells (MCs) are key effectors of the allergic response. Following the cross-linking of IgE receptors (Fc\u03b5RIs), they release crucial inflammatory mediators through degranulation. Although degranulation depends critically on secretory granule (SG) trafficking toward the plasma membrane, the molecular machinery underlying this transport has not been fully characterized.<\/p>\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Objectives:\u00a0<\/strong>This study analyzed the function of Rab44, a large, atypical Rab guanosine triphosphatase highly expressed in MC, in the MC degranulation process.<\/p>\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Methods:\u00a0<\/strong>Murine knockout (KO) mouse models (KO<sup>Rab44<\/sup>\u00a0and DKO<sup>Kif5b\/Rab44<\/sup>) were used to perform passive cutaneous anaphylaxis experiments and analyze granule translocation in bone marrow-derived MCs during degranulation.<\/p>\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Results:\u00a0<\/strong>This study demonstrate that mice lacking Rab44 (KO<sup>Rab44<\/sup>) in their bone marrow-derived MCs are impaired in their ability to translocate and degranulate SGs at the plasma membrane on Fc\u03b5RI stimulation. Accordingly, KO<sup>Rab44<\/sup>\u00a0mice were less sensitive to IgE-mediated passive cutaneous anaphylaxis in vivo. A lack of Rab44 did not impair early Fc\u03b5RI-stimulated signaling pathways, microtubule reorganization, lipid mediator release, or cytokine secretion. Mechanistically, Rab44 appears to interact with and function as part of the previously described kinesin-1-dependent transport pathway.<\/p>\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Conclusions:\u00a0<\/strong>These results highlight a novel role of Rab44 as a regulator of SG transport during degranulation and anaphylaxis acting through the kinesin-1-dependent microtubule transport machinery. Rab44 can thus be considered a potential target for modulating MC degranulation and inhibiting IgE-mediated allergic reactions.<\/p>\r\n<\/div>","paragraphe_en":"<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Background:\u00a0<\/strong>Mast cells (MCs) are key effectors of the allergic response. Following the cross-linking of IgE receptors (Fc\u03b5RIs), they release crucial inflammatory mediators through degranulation. Although degranulation depends critically on secretory granule (SG) trafficking toward the plasma membrane, the molecular machinery underlying this transport has not been fully characterized.<\/p>\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Objectives:\u00a0<\/strong>This study analyzed the function of Rab44, a large, atypical Rab guanosine triphosphatase highly expressed in MC, in the MC degranulation process.<\/p>\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Methods:\u00a0<\/strong>Murine knockout (KO) mouse models (KO<sup>Rab44<\/sup>\u00a0and DKO<sup>Kif5b\/Rab44<\/sup>) were used to perform passive cutaneous anaphylaxis experiments and analyze granule translocation in bone marrow-derived MCs during degranulation.<\/p>\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Results:\u00a0<\/strong>This study demonstrate that mice lacking Rab44 (KO<sup>Rab44<\/sup>) in their bone marrow-derived MCs are impaired in their ability to translocate and degranulate SGs at the plasma membrane on Fc\u03b5RI stimulation. Accordingly, KO<sup>Rab44<\/sup>\u00a0mice were less sensitive to IgE-mediated passive cutaneous anaphylaxis in vivo. A lack of Rab44 did not impair early Fc\u03b5RI-stimulated signaling pathways, microtubule reorganization, lipid mediator release, or cytokine secretion. Mechanistically, Rab44 appears to interact with and function as part of the previously described kinesin-1-dependent transport pathway.<\/p>\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Conclusions:\u00a0<\/strong>These results highlight a novel role of Rab44 as a regulator of SG transport during degranulation and anaphylaxis acting through the kinesin-1-dependent microtubule transport machinery. Rab44 can thus be considered a potential target for modulating MC degranulation and inhibiting IgE-mediated allergic reactions.<\/p>\r\n<\/div>","documents":null},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Rab44 regulates murine mast cell-driven anaphylaxis through kinesin-1-dependent secretory granule translocation - CRI<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/cri1149.fr\/publication\/rab44-regulates-murine-mast-cell-driven-anaphylaxis-through-kinesin-1-dependent-secretory-granule-translocation\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Rab44 regulates murine mast cell-driven anaphylaxis through kinesin-1-dependent secretory granule translocation - CRI\" \/>\n<meta property=\"og:url\" content=\"https:\/\/cri1149.fr\/publication\/rab44-regulates-murine-mast-cell-driven-anaphylaxis-through-kinesin-1-dependent-secretory-granule-translocation\/\" \/>\n<meta property=\"og:site_name\" content=\"CRI\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/CRI-Centre-de-recherche-sur-linflammation-100116118884153\" \/>\n<meta property=\"article:modified_time\" content=\"2025-09-11T14:47:57+00:00\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/cri1149.fr\\\/publication\\\/rab44-regulates-murine-mast-cell-driven-anaphylaxis-through-kinesin-1-dependent-secretory-granule-translocation\\\/\",\"url\":\"https:\\\/\\\/cri1149.fr\\\/publication\\\/rab44-regulates-murine-mast-cell-driven-anaphylaxis-through-kinesin-1-dependent-secretory-granule-translocation\\\/\",\"name\":\"Rab44 regulates murine mast cell-driven anaphylaxis through kinesin-1-dependent secretory granule translocation - 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