LAMTOR1
Description
The LAMTOR1 (late endosomal/lysosomal adaptor, MAPK and MTOR activator 1) is a protein-coding gene located on chromosome 11.
Late endosomal/lysosomal adaptor, MAPK and MTOR activator 1 is a protein that in humans is encoded by the LAMTOR1 gene.
LAMTOR1 is a key component of the Ragulator complex, a multiprotein complex involved in amino acid sensing and activation of mTORC1, a signaling complex that promotes cell growth in response to growth factors, energy levels, and amino acids. The Ragulator is activated by amino acids through a mechanism involving the lysosomal V-ATPase and plays a dual role for the small GTPases Rag: it acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag, and it mediates recruitment of Rag GTPases to the lysosome membrane. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes, where it is in turn activated. LAMTOR1 is directly responsible for anchoring the Ragulator complex to the lysosomal membrane. It wraps around the other subunits of the Ragulator complex to hold them in place and interacts with the Rag GTPases, thereby playing a key role in the recruitment of the mTORC1 complex to lysosomes. LAMTOR1 is also involved in the control of embryonic stem cell differentiation via non-canonical RagC/RRAGC and RagD/RRAGD activation. Together with FLCN, it is necessary to recruit and activate RagC/RRAGC and RagD/RRAGD at the lysosomes and to induce exit of embryonic stem cells from pluripotency via non-canonical, mTOR-independent TFE3 inactivation. It is also required for late endosomes/lysosomes biogenesis and may regulate both the recycling of receptors through endosomes and the MAPK signaling pathway through recruitment of some of its components to late endosomes. LAMTOR1 may be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes. It may also play a role in RHOA activation.
LAMTOR1 is also known as C11orf59, PDRO, Ragulator1, p18, p27RF-Rho.
Associated Diseases
- autosomal recessive nonsyndromic hearing loss 63
- Parkinson disease
- multiple sclerosis
- Alzheimer disease
- lysosomal storage disease
- esophageal cancer
- hearing loss, autosomal recessive
- 46,XX testicular disorder of sex development
- 46,XY complete gonadal dysgenesis
- isolated congenital hypogonadotropic hypogonadism
- 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency
- familial male-limited precocious puberty
- 46,XX ovotesticular disorder of sex development
