Leptin receptors isoforms

Fig. 20.1 Leptin receptor isoforms. Leptin receptor isoforms (Ob-Ra to Ob-Re) are the result of alternative gene splicing. Ob-Rb is considered to be the active isoform for carrying out downstream signaling. The extracellular region of the receptor is comprised of two CK (cytokine receptor domain) and three F3 (fibronectin domain) domains. The extracellular domain is followed by the transmembrane domain. The intracellular region consists of B1 (box 1) and B2 (box 2) for JAK2 binding and STAT (signal transducers and activators of transcription) binding domain.

Uotani, S., Bjorbaek, C., Tomoe, J., and Flier, J. S. 1999. Functional properties of leptin receptor isoforms internalization and degradation of leptin and ligand-induced receptor downregulation. Diabetes 48 279-286. 

Bjorbaek C, Ebnquist JK, Michl P, Ahima RS, van Benren A, McCall AL, Eber JS (1998) Expression of leptin receptor isoforms in rat brain microvessels. Endocrinology 139 3485-3491. 

Figure 2. Expression of leptin receptor isoforms in dairy heifers. (A) Transcript copy number for Ob-R l were measured. (B) Transcript copy number were measured for OB-Ra and OB-Rb and expressed as a percentage of Ob-R Adapted from Thom et al., 2007.

Shigemura N, Miura H, Kusakabe Y, Hino A, Ninomiya Y (2003) Expression of leptin receptor (Ob-R) isoforms and signal transducers and activators of transcription (STATs) mRNAs in the mouse taste buds. Arch Histol Cytol 66 253-260 Shigemura N, Ohta R, Kusakabe Y, Miura H, Hino A, Koyano K, Nakashima K, Ninomiya Y (2004) Leptin modulates behavioral responses to sweet substances by influencing peripheral taste structures. Endocrinology 145 839-847... 

Expression of leptin receptor (Ob-R) isoforms and signal transducers and activators of transcription (STATs) mRNAs in the mouse taste buds. Arch Histol Cytol 66 253-260. 

It is generally accepted that OBRb is the fully competent signal transduction isoform of the receptor, and that the short-form OBRs (a, c, d, f) while capable of signal transduction, do so to a lesser extent (Bjorbaek et al. 1997 Uotani et al. 1999). The major signaling pathway activated by leptin binding to OBRb is the Janus kinase... 

Five truncated receptors have been identified in rodents (Ahima and Flier, 2000). These isoforms have the same exact extracellular binding domain as Ob-Rb, but differ in lacking all of the other 2 domains (Ob-Re) or most of the cytoplasmic signalling domain (Ob-Ra, Ob-Rc, Ob-Rd and Ob-Rf). Accordingly, they all bind leptin perfectly well but fail to initiate significant signalling. Information on these truncated isoforms is limited in domestic species, except for the Ob-Ra isoform which has been found in most of these animals. 

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