{"id":284904,"date":"2024-08-30T09:20:06","date_gmt":"2024-08-30T07:20:06","guid":{"rendered":"https:\/\/dhcp205002.cbm.uam.es\/?page_id=284904"},"modified":"2026-03-27T08:59:43","modified_gmt":"2026-03-27T07:59:43","slug":"physiopathological-aspects-of-glycine-transporters-in-glycinergic-neurotransmission-hyperekplexia-and-pain","status":"publish","type":"page","link":"https:\/\/www.cbm.uam.es\/index.php\/scientific-programs\/physiological-and-pathological-processes\/molecular-neuropathology\/physiopathological-aspects-of-glycine-transporters-in-glycinergic-neurotransmission-hyperekplexia-and-pain\/","title":{"rendered":"Physiopathological aspects of glycine transporters in glycinergic neurotransmission: hyperekplexia and pain"},"content":{"rendered":"

[et_pb_section fb_built=”1″ _builder_version=”4.27.0″ _module_preset=”default” background_color=”#34609B” background_image=”https:\/\/www.cbm.uam.es\/wp-content\/uploads\/2024\/07\/iStock-1356994685small-scaled.jpg” background_position=”bottom_center” background_vertical_offset=”32%” min_height=”352px” height=”294px” da_disable_devices=”off|off|off” global_colors_info=”{}” da_is_popup=”off” da_exit_intent=”off” da_has_close=”on” da_alt_close=”off” da_dark_close=”off” da_not_modal=”on” da_is_singular=”off” da_with_loader=”off” da_has_shadow=”on”][et_pb_row column_structure=”2_5,3_5″ use_custom_gutter=”on” gutter_width=”4″ _builder_version=”4.23.4″ _module_preset=”default” background_color=”RGBA(255,255,255,0)” custom_margin=”61px||||false|false” custom_padding=”||0px|||” global_colors_info=”{}”][et_pb_column type=”2_5″ _builder_version=”4.23.4″ _module_preset=”default” background_color=”rgba(52,96,155,0.83)” custom_padding=”50px||50px|50px|false|false” border_radii=”on|15px|15px|15px|15px” global_colors_info=”{}”][et_pb_text _builder_version=”4.25.0″ _module_preset=”default” text_text_color=”#FFFFFF” custom_margin=”0px||10px||false|false” custom_padding=”0px||0px||false|false” global_colors_info=”{}”]<\/p>\n

Scientific Program<\/p>\n

[\/et_pb_text][et_pb_heading title=”Physiological and pathological processes” _builder_version=”4.27.0″ _module_preset=”default” title_font=”Montserrat||||||||” title_text_color=”#FFFFFF” title_font_size=”43px” global_colors_info=”{}”][\/et_pb_heading][\/et_pb_column][et_pb_column type=”3_5″ _builder_version=”4.23.4″ _module_preset=”default” custom_padding=”157px||||false|false” global_colors_info=”{}”][et_pb_text _builder_version=”4.25.0″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n

UNITS IN THIS PROGRAM
\n<\/span><\/h4>\n
\n

\nMolecular neuropathology<\/a><\/span>\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0Metabolic and signaling networks in disease<\/a><\/span><\/h6>\n

[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.23.4″ _module_preset=”default” background_enable_image=”off” background_size=”custom” background_image_height=”84%” background_position=”bottom_right” custom_margin=”||0px||false|false” custom_padding=”||0px||false|false” da_disable_devices=”off|off|off” global_colors_info=”{}” da_is_popup=”off” da_exit_intent=”off” da_has_close=”on” da_alt_close=”off” da_dark_close=”off” da_not_modal=”on” da_is_singular=”off” da_with_loader=”off” da_has_shadow=”on”][et_pb_row _builder_version=”4.23.4″ _module_preset=”default” custom_margin=”||0px||false|false” custom_padding=”||0px||false|false” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_heading title=”RESEARCH GROUP” _builder_version=”4.25.0″ _module_preset=”default” title_level=”h5″ title_text_color=”#13B5BD” custom_margin=”50px||0px||false|false” global_colors_info=”{}”][\/et_pb_heading][et_pb_blurb title=”Physiopathological aspects of glycine transporters in glycinergic neurotransmission: hyperekplexia and pain” use_icon=”on” font_icon=”||divi||400″ icon_color=”#13B5BD” icon_placement=”left” image_icon_width=”26px” content_max_width=”1100px” content_max_width_tablet=”1100px” content_max_width_last_edited=”off|desktop” _builder_version=”4.27.0″ header_level=”h1″ header_font=”Montserrat||||||||” header_text_color=”#000000″ header_font_size=”29px” header_line_height=”1.4em” body_font=”||||||||” body_font_size=”15px” body_line_height=”1.8em” image_icon_custom_margin=”6px||||false|false” background_layout=”dark” custom_margin=”|||” custom_padding=”||14px||false|false” animation_style=”slide” animation_direction=”right” animation_intensity_slide=”10%” animation=”off” image_max_width=”64px” global_colors_info=”{}”][\/et_pb_blurb][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.23.4″ _module_preset=”default” background_color=”rgba(175,218,249,0.18)” custom_padding=”0px||0px||false|false” da_disable_devices=”off|off|off” global_colors_info=”{}” da_is_popup=”off” da_exit_intent=”off” da_has_close=”on” da_alt_close=”off” da_dark_close=”off” da_not_modal=”on” da_is_singular=”off” da_with_loader=”off” da_has_shadow=”on”][et_pb_row column_structure=”1_4,1_4,1_4,1_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_column type=”1_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_image src=”\/imgs\/22.jpg” title_text=”logoRecurso 7″ align=”right” module_class=”roundedImg” _builder_version=”4.25.0″ _module_preset=”default” global_colors_info=”{}”][\/et_pb_image][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_heading title=”Beatriz L\u00f3pez Corcuera” _builder_version=”4.27.4″ _module_preset=”default” title_level=”h3″ title_text_align=”left” title_text_color=”#008C93″ global_colors_info=”{}”][\/et_pb_heading][et_pb_text _builder_version=”4.27.4″ _module_preset=”default” custom_margin=”-27px||||false|false” link_option_url_new_window=”on” global_colors_info=”{}”]<\/p>\n

ORCID<\/a>
<\/a><\/p>\n

[\/et_pb_text][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_image src=”\/imgs\/24.jpg” title_text=”logoRecurso 7″ align=”right” module_class=”roundedImg” _builder_version=”4.25.0″ _module_preset=”default” global_colors_info=”{}”][\/et_pb_image][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_heading title=”Francisco Zafra G\u00f3mez” _builder_version=”4.27.4″ _module_preset=”default” title_level=”h3″ title_text_align=”left” title_text_color=”#008C93″ global_colors_info=”{}”][\/et_pb_heading][et_pb_text _builder_version=”4.27.4″ _module_preset=”default” custom_margin=”-27px||||false|false” link_option_url_new_window=”on” global_colors_info=”{}”]<\/p>\n

ORCID<\/a>
<\/a><\/p>\n

[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.23.4″ _module_preset=”default” background_color=”#13B5BD” custom_margin=”0px||0px||false|false” custom_padding=”0px||0px||false|false” da_disable_devices=”off|off|off” global_colors_info=”{}” da_is_popup=”off” da_exit_intent=”off” da_has_close=”on” da_alt_close=”off” da_dark_close=”off” da_not_modal=”on” da_is_singular=”off” da_with_loader=”off” da_has_shadow=”on”][et_pb_row column_structure=”1_3,1_3,1_3″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_column type=”1_3″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_button button_url=”#investiga” button_text=”Research” button_alignment=”center” _builder_version=”4.25.0″ _module_preset=”default” custom_button=”on” button_bg_color=”#34609B” animation_style=”zoom” global_colors_info=”{}”][\/et_pb_button][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_button button_url=”#personal” button_text=”Group members” button_alignment=”center” _builder_version=”4.25.0″ _module_preset=”default” custom_button=”on” button_bg_color=”#34609B” custom_padding=”|44px||44px|false|true” animation_style=”zoom” global_colors_info=”{}”][\/et_pb_button][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_button button_url=”#publica” button_text=”Publications” button_alignment=”center” _builder_version=”4.25.0″ _module_preset=”default” custom_button=”on” button_bg_color=”#34609B” animation_style=”zoom” global_colors_info=”{}”][\/et_pb_button][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.23.4″ _module_preset=”default” background_enable_image=”off” background_size=”custom” background_image_height=”84%” background_position=”bottom_right” custom_margin=”0px||0px||false|false” custom_padding=”0px||15px||false|false” da_disable_devices=”off|off|off” global_colors_info=”{}” da_is_popup=”off” da_exit_intent=”off” da_has_close=”on” da_alt_close=”off” da_dark_close=”off” da_not_modal=”on” da_is_singular=”off” da_with_loader=”off” da_has_shadow=”on”][et_pb_row column_structure=”1_2,1_2″ use_custom_gutter=”on” gutter_width=”2″ _builder_version=”4.23.4″ _module_preset=”default” custom_margin=”20px||||false|false” custom_padding=”||||false|false” global_colors_info=”{}”][et_pb_column type=”1_2″ _builder_version=”4.23.4″ _module_preset=”default” global_colors_info=”{}”][et_pb_text admin_label=”resumen” module_id=”resumen” module_class=”resumen” _builder_version=”4.27.4″ _module_preset=”default” text_font_size=”15px” text_line_height=”1.8em” background_color=”#f1f8fe” custom_padding=”20px|20px|20px|20px|true|false” border_width_top=”1px” border_color_top=”#008C93″ border_width_bottom=”1px” border_color_bottom=”#008C93″ global_colors_info=”{}”]<\/p>\n

Glycine is the main inhibitory neurotransmitter in caudal central nervous system and exerts sensorimotor control and nociceptive processing. The dysfunction of glycinergic inhibition leads to two main diseases: hyperekplexia and pathological pain. We study, at the cellular and molecular levels, physiology and pathologies of glycinergic neurotransmission to provide therapeutic tools. We also extend our expertise to other neurotransmitter transporters.<\/p>\n

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Our group studies glycinergic neurotransmission in health and disease, focusing on hyperekplexia, a rare neurological syndrome caused by mutations in key proteins such as the glycine transporter GlyT2 (SLC6A5<\/em> gene), and pain. Our aim is to understand how GlyT2 mutations affect patients\u2019 physiology and to develop strategies to rescue mutant phenotypes or to produce modulatory ligands with diverse applications, including analgesia.<\/p>\n

Using bioinformatics and several experimental models (cell lines, neuronal cultures, mutant mice, Xenopus<\/em> oocytes, Zebrafish), our research investigates GlyT2 structure, trafficking, regulation, and interactions. Proteomics approaches following a new version of the proximity labelling technique suitable for its use in native tissue is being optimized to identify new GlyT2 partners influencing its function.<\/p>\n

Recently, we have identified a novel GlyT2 variant found in a child patient with hyperekplexia displaying a new pathogenic mechanism: it is a loss-of-function variant with respect to transporter activity, but a gain-of-function variant that alters cellular proteostasis, activating the unfolded protein response (UPR) and interfering with processes occurring in lipid rafts.\u00a0<\/p>\n

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Another research focus aims to understand the mechanistic basis for the heightened severity of hyperekplexia symptoms during the perinatal period. We examined the role of GlyT2 in neuronal differentiation using the PC12 cell model and found GlyT2 is clearly implicated in growth cone progression and differentiation of PC12 cells into neurons by increasing internal calcium and binding to growth cone proteins.<\/p>\n

We also found GlyT2 is regulated by the Hedgehog pathway, what can be emulated by D2 dopamine receptor agonists, indicating glycinergic interneurons containing GlyT2 receive dopaminergic inputs in response to the Hedgehog pathway activation. The biological significance of this regulation in the control of peripherally acting neuronal nuclei is being further investigated.<\/p>\n

Finally, we are also interested in the molecular mechanisms that regulate the activity of other neurotransmitter transporters including those for GABA or dopamine. We study the genetic alterations in these transporters\u2019 genes, which produce defective proteins either in their transport mechanism or in their intracellular trafficking. We conducted structure-function studies, intracellular trafficking analysis and interactors identification.<\/p>\n

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A New GlyT2 Variant Associated with Hyperekplexia<\/h3>\n

Jorge Sarmiento-Jim\u00e9nez et al.<\/p>\n

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Experimental and Bioinformatic Insights into the Effects of Epileptogenic Variants on the Function and Trafficking of the GABA Transporter GAT-1<\/h3>\n

Dolores Piniella et al.<\/p>\n

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Rescue of two trafficking-defective variants of the neuronal glycine transporter GlyT2 associated to hyperekplexia<\/h3>\n

Andr\u00e9s de la Rocha-Mu\u00f1oz et al.<\/p>\n

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Functional crosstalk of the glycine transporter GlyT1 and NMDA receptors<\/h3>\n

Dolores Piniella et al.<\/p>\n

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Cargando publicaciones…<\/div>\n