LRTM2 AND ITS POTENTIAL BINDING PARTNERS: INSIGHTS INTO THEIR ROLES IN STRIATAL MEDIUM SPINY NEURONS

Abstract Neural leucine-rich-repeat (LRR) transmembrane superfamily proteins have emerged as pivotal players in neural health and pathology. Notably, proteins characterized by LRR domains with no other discernible extracellular motifs have been established as crucial for synaptogenesis and synaptic maintenance. Lrtm2, a member of this LRR-exclusive group, displays pronounced expression in the striatum, globus pallidus, and substantia nigra pars reticulata of mouse brains, with its protein levels rising during postnatal development. Past research indicated that Lrtm2-deficient mice presented with modified motor functions and fluctuations in dopamine metabolite levels within the striatum and associated regions. Our study aimed to elucidate Lrtm2's role in striatal medium spiny neurons. Our findings show alterations in the distribution of proteins pivotal for neurotransmitter regulation in the striatonigral GABAergic pathway of Lrtm2-deficient mice. These observations led us to hypothesize Lrtm2's involvement in macromolecular trafficking within striatal neurons. To further discern the molecular mechanisms by which Lrtm2 may regulate macromolecular transport, we verified the co-localization of Lrtm2 and its potential binding partners in vivo.