Protein Trafficking or Cell Signaling: A Dilemma for the Adaptor Protein TOM1

Abstract

Lysosomal degradation of ubiquitinated transmembrane protein receptors (cargo) relies on the function of Endosomal Sorting Complex Required for Transport (ESCRT) protein complexes. The ESCRT machinery is comprised of five unique oligomeric complexes with distinct functions. Target of Myb1 (TOM1) is an ESCRT protein involved in the initial steps of endosomal cargo sorting. To exert its function, TOM1 associates with ubiquitin moieties on the cargo via its VHS and GAT domains. Several ESCRT proteins, including TOLLIP, Endofin, and Hrs, have been reported to form a complex with TOM1 at early endosomal membrane surfaces, which may potentiate the role of TOM1 in cargo sorting. More recently, it was found that TOM1 is involved in other physiological processes, including autophagy, immune responses, and neuroinflammation, which crosstalk with its endosomal cargo sorting function. Alteration of TOM1 function has emerged as a phosphoinositide-dependent survival mechanism for bacterial infections and cancer progression. Based on current knowledge of TOM1-dependent cellular processes, this review illustrates how TOM1 functions in coordination with an array of protein partners under physiological and pathological scenarios.

Broad-spectrum chemicals block ROS detoxification to prevent plant fungal invasion

“…In higher plants and mammalians, Tom1 and Tol proteins are involved in a variety of physiological processes, which crosstalk with their endosomal cargo sorting function. [22][23][24][25] However, the Tom1 family has not yet been characterized in filamentous fungi, and its regulatory role in protein secretion and virulence of plant fungal pathogens remain elusive.…”

The PH Domain and C-Terminal polyD Motif of Phafin2 Exhibit a Unique Concurrence in Animals

“…Other protein domains, such as V ps27, H rs, S TAM (VHS), phosphatidylinositol 3- and 4-kinases, and ub iquitin- a ssociated (UBA)-like domains, were found to be encoded together with the FYVE domains ( Table S1 , Figure 4 and Figure S1, and Supplementary Files S3 and S4 ). Whereas eukaryotic VHS domains are involved in vesicular trafficking by either ubiquitinated cargo recognition or through phosphorylated receptor binding [ 30 ], bacterial VHS domains facilitate the subcellular localization of protein effectors [ 31 ]. Likewise, UBA-like domains are associated with the ubiquitin/proteasome pathway in eukaryotes, but are uncommon domains of unknown function in bacteria [ 32 , 33 ].…”

Synovial Fluid Profile Dictates Nanopracticle Uptake into Cartilage- Implications of the Protein Corona for Novel Arthitis Treatments

“…Patient synovial fluids were characterized by a significant differential expression proteins such as TOM1 in OA, and TOLLIP in RA. Literature has recently linked TOM1 protein with endosomal transport, impaired autophagy, and immune response, thus linking TOM1 to pathologies such RA and OA 18,19 .…”