Sandbox Reserved 1648: Difference between revisions

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== '''Structure''' ==

The leptin receptor protein exists in different forms. Up to now, six ObR isoforms are known named ObRa to ObRf. They are produced by alternative splicing or ectodomain shedding. <ref name="refl"> doi: 10.3389/fendo.2017.00030 <ref/>

The leptin receptor protein exists in different forms. Up to now, six ObR isoforms are known named ObRa to ObRf. They are produced by alternative splicing or ectodomain shedding <ref name="refl"> doi: 10.3389/fendo.2017.00030 </ref> .

It consists of an '''extracellular chain''' of 816 amino acids, a '''transmembrane domain''' of 23 amino acids and a '''cytoplasmic domain''' <ref name="ref1"> Le récepteur de la leptine appartient à la famille des récepteurs de cytokines : http://www.ipubli.inserm.fr/bitstream/handle/10608/746/1996_3_386.pdf?sequence=1 </ref> <ref name="ref2"> La leptine : une nouvelle hormone hypo-insulinémiante ? : http://ipubli-inserm.inist.fr/bitstream/handle/10608/532/MS_1997_10_1200.pdf?sequence=1</ref>.

These proteins exists in a '''long form''' and in a '''short forms''' with a cytoplasmic domain of variable size : 302 amino acids for the long form ObRb and 30-40 amino acids for short forms ObRa, ObRc, ObRd, ObRf. There is also a soluble form ObRe. <ref name ="refl">

These proteins exists in a '''long form''' and in a '''short forms''' with a cytoplasmic domain of variable size : 302 amino acids for the long form ObRb and 30-40 amino acids for short forms ObRa, ObRc, ObRd, ObRf. There is also a soluble form ObRe <ref name ="refl"> </ref> .

All isoforms have an identical extracellular domain containing 6 functional domains :

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- two CRH domains (a distal membrane homology of the first cytokine receptor '''CHR1''' and a second homology of the cytokine receptor '''CRH2''')

- an immunoglobuline-like domain ('''IGD'')

- an immunoglobuline-like domain ('''IGD''')

- two additional membrane-proximal fibronectin type III ('''FN III''') domains <ref>DOI:https://doi.org/10.1016/j.str.2012.01.019<ref/> <ref name="refl">.

ObR is heavily glycosylated causing an increase of 30-70 kDa in molecular weight. <ref name="refl">

ObR is heavily glycosylated causing an increase of 30-70 kDa in molecular weight <ref name="refl"> </ref> .

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Leptin receptors are found in different regions depending on the short or long form of the protein.

The long form (Ob-Rl) is mainly present in the [https://en.wikipedia.org/wiki/Hypothalamus '''hypothalamus'''], notably in the [https://en.wikipedia.org/wiki/Arcuate_nucleus arcuate nucleus], [https://en.wikipedia.org/wiki/Dorsomedial_hypothalamic_nucleus dorsomedial] and [https://en.wikipedia.org/wiki/Ventromedial_nucleus_of_the_hypothalamus ventromedial] nuclei, and in the paraventricular nucleus ([https://en.wikipedia.org/wiki/Paraventricular_nucleus_of_hypothalamus PVN]) <ref name="ref4"> Leptin : https://www.eurofins-biomnis.com/referentiel/liendoc/precis/LEPTINE.pdf </ref> <ref name="ref5"> La leptine : votre cerveau, l'appétit et l'obésité : https://www.societe-neuroendocrinologie.fr/Breves/03-La-leptine-votre-cerveau-l-appetit-et-l-obesite </ref> <ref name="ref6"> La leptine : une clé pour la reproduction : http://www.ipubli.inserm.fr/bitstream/handle/10608/1310/1999_2_191.pdf?sequence=2 </ref>. It is also found in lesser amounts in the [https://en.wikipedia.org/wiki/Pancreatic_islets '''islets of Langerhans'''] in ~~mouses~~, as well as in the '''liver''', '''spleen''', heart''', [https://en.wikipedia.org/wiki/White_adipose_tissue '''white fat'''], [https://en.wikipedia.org/wiki/Lymph_node '''lymph node'''], [https://en.wikipedia.org/wiki/Jejunum '''jejunum'''] and [https://en.wikipedia.org/wiki/Hematopoietic_stem_cell '''hematopoietic stem cells''']<ref name="ref2"/> <ref name="ref7"> ~~Leptine et diabète~~ : ~~http~~://www.~~exobiologie~~.~~info~~/~~diabete~~/~~24%20leptine~~.~~pdf~~ </ref>.

The '''long form''' (Ob-Rl) is mainly present in the [https://en.wikipedia.org/wiki/Hypothalamus '''hypothalamus'''], notably in the [https://en.wikipedia.org/wiki/Arcuate_nucleus arcuate nucleus], [https://en.wikipedia.org/wiki/Dorsomedial_hypothalamic_nucleus dorsomedial] and [https://en.wikipedia.org/wiki/Ventromedial_nucleus_of_the_hypothalamus ventromedial] nuclei, and in the paraventricular nucleus ([https://en.wikipedia.org/wiki/Paraventricular_nucleus_of_hypothalamus PVN]) <ref name="ref4"> Leptin : https://www.eurofins-biomnis.com/referentiel/liendoc/precis/LEPTINE.pdf </ref> <ref name="ref5"> La leptine : votre cerveau, l'appétit et l'obésité : https://www.societe-neuroendocrinologie.fr/Breves/03-La-leptine-votre-cerveau-l-appetit-et-l-obesite </ref> <ref name="ref6"> La leptine : une clé pour la reproduction : http://www.ipubli.inserm.fr/bitstream/handle/10608/1310/1999_2_191.pdf?sequence=2 </ref>. It is also found in lesser amounts in the [https://en.wikipedia.org/wiki/Pancreatic_islets '''islets of Langerhans'''] in mice, as well as in the '''liver''', '''spleen''', '''heart''', [https://en.wikipedia.org/wiki/White_adipose_tissue '''white fat'''], [https://en.wikipedia.org/wiki/Lymph_node '''lymph node'''], [https://en.wikipedia.org/wiki/Jejunum '''jejunum'''] and [https://en.wikipedia.org/wiki/Hematopoietic_stem_cell '''hematopoietic stem cells''']<ref name="ref2"/> <ref name="ref7"> Hormonal Regulation of Fuel Metabolism : https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/leptin-receptor </ref>.

The '''short-form''' (Ob-Ra) is located primarily in the '''lungs''', '''kidneys''' and '''islets of Langerhans''' <ref name="ref4"/>. It is also present in smaller quantities in the brain at the '''hypothalamus'''.<ref name="ref5"/> Ob-Ra is the only form of the protein found in '''ovaries'''. Short form serve to facilitate passage of leptin across the blood cerebrospinal fluid barrier.

~~The short-form (Ob-Ra) is located primarily~~ in the '''~~lungs~~''', '''~~kidneys~~''' ~~and~~ '''~~islets of Langerhans~~''' ~~<ref name="ref4"/>~~. ~~It is also present~~ in ~~smaller quantities~~ in ~~the brain at the~~ '''~~hypothalamus~~'''.<ref name="~~ref5~~"/> ~~Ob-Ra is the only form of the protein found in '''ovaries'''~~.

Leptin receptors play a role in the regulation of body weight and blunt the drive for food intake, so they are found in '''adipocytes''', '''muscles''', '''hypothalamus'''. Leptin receptors intervene in '''gonads''' to support fertility especially in '''Leydig cells''' in mice, in '''bone marrow''' to promote hematopoiesis and actions in capillary '''endothelium''' to increase angiogenesis <ref name="ref7"> </ref>.

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@@ Line 11: / Line 11: @@
 == '''Structure''' ==
-The leptin receptor protein exists in different forms. Up to now, six ObR isoforms are known named ObRa to ObRf. They are produced by alternative splicing or ectodomain shedding. <ref name="refl"> doi: 10.3389/fendo.2017.00030 <ref/>
+The leptin receptor protein exists in different forms. Up to now, six ObR isoforms are known named ObRa to ObRf. They are produced by alternative splicing or ectodomain shedding <ref name="refl"> doi: 10.3389/fendo.2017.00030 </ref> .
 It consists of an '''extracellular chain''' of 816 amino acids, a '''transmembrane domain''' of 23 amino acids and a '''cytoplasmic domain''' <ref name="ref1"> Le récepteur de la leptine appartient à la famille des récepteurs de cytokines : http://www.ipubli.inserm.fr/bitstream/handle/10608/746/1996_3_386.pdf?sequence=1 </ref> <ref name="ref2"> La leptine : une nouvelle hormone hypo-insulinémiante ? :  http://ipubli-inserm.inist.fr/bitstream/handle/10608/532/MS_1997_10_1200.pdf?sequence=1</ref>.
-These proteins exists in a '''long form''' and in a '''short forms''' with a cytoplasmic domain of variable size : 302 amino acids for the long form ObRb and 30-40 amino acids for short forms ObRa, ObRc, ObRd, ObRf. There is also a soluble form ObRe. <ref name ="refl">
+These proteins exists in a '''long form''' and in a '''short forms''' with a cytoplasmic domain of variable size : 302 amino acids for the long form ObRb and 30-40 amino acids for short forms ObRa, ObRc, ObRd, ObRf. There is also a soluble form ObRe <ref name ="refl"> </ref> .
 All isoforms have an identical extracellular domain containing 6 functional domains :
@@ Line 20: / Line 20: @@
 - two CRH domains (a distal membrane homology of the first cytokine receptor '''CHR1''' and a second homology of the cytokine receptor '''CRH2''')
-- an immunoglobuline-like domain ('''IGD'')
+- an immunoglobuline-like domain ('''IGD''')
 - two additional membrane-proximal fibronectin type III ('''FN III''') domains <ref>DOI:https://doi.org/10.1016/j.str.2012.01.019<ref/> <ref name="refl">.
-ObR is heavily glycosylated causing an increase of 30-70 kDa in molecular weight. <ref name="refl">
+ObR is heavily glycosylated causing an increase of 30-70 kDa in molecular weight <ref name="refl"> </ref> .
@@ Line 31: / Line 30: @@
 Leptin receptors are found in different regions depending on the short or long form of the protein.
-The long form (Ob-Rl) is mainly present in the [https://en.wikipedia.org/wiki/Hypothalamus '''hypothalamus'''], notably in the [https://en.wikipedia.org/wiki/Arcuate_nucleus arcuate nucleus], [https://en.wikipedia.org/wiki/Dorsomedial_hypothalamic_nucleus dorsomedial] and [https://en.wikipedia.org/wiki/Ventromedial_nucleus_of_the_hypothalamus ventromedial] nuclei, and in the paraventricular nucleus ([https://en.wikipedia.org/wiki/Paraventricular_nucleus_of_hypothalamus PVN]) <ref name="ref4"> Leptin : https://www.eurofins-biomnis.com/referentiel/liendoc/precis/LEPTINE.pdf </ref> <ref name="ref5"> La leptine : votre cerveau, l'appétit et l'obésité :  https://www.societe-neuroendocrinologie.fr/Breves/03-La-leptine-votre-cerveau-l-appetit-et-l-obesite </ref> <ref name="ref6"> La leptine : une clé pour la reproduction : http://www.ipubli.inserm.fr/bitstream/handle/10608/1310/1999_2_191.pdf?sequence=2 </ref>. It is also found in lesser amounts in the [https://en.wikipedia.org/wiki/Pancreatic_islets '''islets of Langerhans'''] in mouses, as well as in the '''liver''', '''spleen''', heart''', [https://en.wikipedia.org/wiki/White_adipose_tissue '''white fat'''], [https://en.wikipedia.org/wiki/Lymph_node '''lymph node'''], [https://en.wikipedia.org/wiki/Jejunum '''jejunum'''] and [https://en.wikipedia.org/wiki/Hematopoietic_stem_cell '''hematopoietic stem cells''']<ref name="ref2"/> <ref name="ref7"> Leptine et diabète : http://www.exobiologie.info/diabete/24%20leptine.pdf </ref>.
+The '''long form''' (Ob-Rl) is mainly present in the [https://en.wikipedia.org/wiki/Hypothalamus '''hypothalamus'''], notably in the [https://en.wikipedia.org/wiki/Arcuate_nucleus arcuate nucleus], [https://en.wikipedia.org/wiki/Dorsomedial_hypothalamic_nucleus dorsomedial] and [https://en.wikipedia.org/wiki/Ventromedial_nucleus_of_the_hypothalamus ventromedial] nuclei, and in the paraventricular nucleus ([https://en.wikipedia.org/wiki/Paraventricular_nucleus_of_hypothalamus PVN]) <ref name="ref4"> Leptin : https://www.eurofins-biomnis.com/referentiel/liendoc/precis/LEPTINE.pdf </ref> <ref name="ref5"> La leptine : votre cerveau, l'appétit et l'obésité :  https://www.societe-neuroendocrinologie.fr/Breves/03-La-leptine-votre-cerveau-l-appetit-et-l-obesite </ref> <ref name="ref6"> La leptine : une clé pour la reproduction : http://www.ipubli.inserm.fr/bitstream/handle/10608/1310/1999_2_191.pdf?sequence=2 </ref>. It is also found in lesser amounts in the [https://en.wikipedia.org/wiki/Pancreatic_islets '''islets of Langerhans'''] in mice, as well as in the '''liver''', '''spleen''', '''heart''', [https://en.wikipedia.org/wiki/White_adipose_tissue '''white fat'''], [https://en.wikipedia.org/wiki/Lymph_node '''lymph node'''], [https://en.wikipedia.org/wiki/Jejunum '''jejunum'''] and [https://en.wikipedia.org/wiki/Hematopoietic_stem_cell '''hematopoietic stem cells''']<ref name="ref2"/> <ref name="ref7"> Hormonal Regulation of Fuel Metabolism : https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/leptin-receptor </ref>.
+The '''short-form''' (Ob-Ra) is located primarily in the '''lungs''', '''kidneys''' and '''islets of Langerhans''' <ref name="ref4"/>. It is also present in smaller quantities in the brain at the '''hypothalamus'''.<ref name="ref5"/> Ob-Ra is the only form of the protein found in '''ovaries'''. Short form serve to facilitate passage of leptin across the blood cerebrospinal fluid barrier.
-The short-form (Ob-Ra) is located primarily in the '''lungs''', '''kidneys''' and '''islets of Langerhans''' <ref name="ref4"/>. It is also present in smaller quantities in the brain at the '''hypothalamus'''.<ref name="ref5"/> Ob-Ra is the only form of the protein found in '''ovaries'''.
+Leptin receptors play a role in the regulation of body weight and blunt the drive for food intake, so they are found in '''adipocytes''', '''muscles''', '''hypothalamus'''. Leptin receptors intervene in '''gonads''' to support fertility especially in '''Leydig cells''' in mice, in '''bone marrow''' to promote hematopoiesis and actions in capillary '''endothelium''' to increase angiogenesis <ref name="ref7"> </ref>.