Taxonomic distribution of proteins containing LAMTOR domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing LAMTOR domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessaryfor its activation by amino acids.

Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM
Cell. 2010; 141: 290-303

The mTORC1 kinase promotes growth in response to growth factors, energy levels,and amino acids, and its activity is often deregulated in disease. The RagGTPases interact with mTORC1 and are proposed to activate it in response to aminoacids by promoting mTORC1 translocation to a membrane-bound compartment thatcontains the mTORC1 activator, Rheb. We show that amino acids induce the movementof mTORC1 to lysosomal membranes, where the Rag proteins reside. A complexencoded by the MAPKSP1, ROBLD3, and c11orf59 genes, which we term Ragulator,interacts with the Rag GTPases, recruits them to lysosomes, and is essential for mTORC1 activation. Constitutive targeting of mTORC1 to the lysosomal surface issufficient to render the mTORC1 pathway amino acid insensitive and independent ofRag and Ragulator, but not Rheb, function. Thus, Rag-Ragulator-mediatedtranslocation of mTORC1 to lysosomal membranes is the key event in amino acidsignaling to mTORC1.

A novel protein associated with membrane-type 1 matrix metalloproteinase bindsp27(kip1) and regulates RhoA activation, actin remodeling, and matrigel invasion.

Hoshino D, Tomari T, Nagano M, Koshikawa N, Seiki M
J Biol Chem. 2009; 284: 27315-26

Pericellular proteolysis by membrane-type 1 matrix metalloproteinase (MT1-MMP)plays a pivotal role in tumor cell invasion. Localization of MT1-MMP at theinvasion front of cells, e.g. on lamellipodia and invadopodia, has to beregulated in coordination with reorganization of the actin cytoskeleton. However,little is known about how such invasion-related actin structures are regulated atthe sites where MT1-MMP localizes. During analysis of MT1-MMP-associatedproteins, we identified a heretofore uncharacterized protein. This protein, whichwe call p27RF-Rho, enhances activation of RhoA by releasing it from inhibition byp27(kip1) and thereby regulates actin structures. p27(kip1) is a well known cell cycle regulator in the nucleus. In contrast, cytoplasmic p27(kip1) has beendemonstrated to bind GDP-RhoA and inhibit GDP-GTP exchange mediated by guaninenucleotide exchange factors. p27RF-Rho binds p27(kip1) and prevents p27(kip1)from binding to RhoA, thereby freeing the latter for activation. Knockdown ofp27RF-Rho expression renders cells resistant to RhoA activation stimuli, whereas overexpression of p27RF-Rho sensitizes cells to such stimulation. p27RF-Rhoexhibits a punctate distribution in invasive human tumor cell lines. Stimulation of the cells with lysophosphatidic acid induces activation of RhoA and inducesthe formation of punctate actin structures within foci of p27RF-Rho localization.Some of the punctate actin structures co-localize with MT1-MMP and cortactin.Down-regulation of p27RF-Rho prevents both redistribution of actin into thepunctate structures and tumor cell invasion. Thus, p27RF-Rho is a new potentialtarget for cancer therapy development.

The novel lipid raft adaptor p18 controls endosome dynamics by anchoring theMEK-ERK pathway to late endosomes.

Nada S, Hondo A, Kasai A, Koike M, Saito K, Uchiyama Y, Okada M
EMBO J. 2009; 28: 477-89

The regulation of endosome dynamics is crucial for fundamental cellularfunctions, such as nutrient intake/digestion, membrane protein cycling, cellmigration and intracellular signalling. Here, we show that a novel lipid raftadaptor protein, p18, is involved in controlling endosome dynamics by anchoringthe MEK1-ERK pathway to late endosomes. p18 is anchored to lipid rafts of lateendosomes through its N-terminal unique region. p18(-/-) mice are embryoniclethal and have severe defects in endosome/lysosome organization and membraneprotein transport in the visceral endoderm. p18(-/-) cells exhibit apparentdefects in endosome dynamics through perinuclear compartment, such as aberrantdistribution and/or processing of lysosomes and impaired cycling ofRab11-positive recycling endosomes. p18 specifically binds to the p14-MP1complex, a scaffold for MEK1. Loss of p18 function excludes the p14-MP1 complexfrom late endosomes, resulting in a downregulation of the MEK-ERK activity. Theseresults indicate that the lipid raft adaptor p18 is essential for anchoring theMEK-ERK pathway to late endosomes, and shed new light on a role of endosomalMEK-ERK pathway in controlling endosome dynamics.