更新于：2024-11-01

TAMALIN

更新于：2024-11-01

基本信息

别名

General receptor for phosphoinositides 1-associated scaffold protein、GRASP、GRP1-associated scaffold protein

+ [3]

简介

Plays a role in intracellular trafficking and contributes to the macromolecular organization of group 1 metabotropic glutamate receptors (mGluRs) at synapses.

关联

项与 TAMALIN 相关的药物

TAM/MET inhibitors (Array BioPharma)

TAM/MET抑制剂(Array BioPharma)

靶点

METTL1 x TAMALIN

作用机制

METTL1 抑制剂 [+1]

在研机构

Array BioPharma, Inc.

原研机构

Array BioPharma, Inc.

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TAMALIN 相关的临床结果

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100 项与 TAMALIN 相关的转化医学

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0 项与 TAMALIN 相关的专利（医药）

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118

项与 TAMALIN 相关的文献（医药）

2024-09-01·Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

Exploring liquid-liquid phase separation in the organisation of Golgi matrix proteins

Article

作者: Mendes, Luis Felipe S ; Oliveira, Carolina G ; Simões, Kevin F ; Costa-Filho, Antonio J ; Kava, Emanuel

The Golgi apparatus is a critical organelle in protein sorting and lipid metabolism. Characterized by its stacked, flattened cisternal structure, the Golgi exhibits distinct polarity with its cis- and trans-faces orchestrating various protein maturation and transport processes. At the heart of its structural integrity and organisation are the Golgi Matrix Proteins (GMPs), predominantly comprising Golgins and GRASPs. These proteins contribute to this organelle's unique stacked and polarized structure and ensure the precise localization of Golgi-resident enzymes, which is crucial for accurate protein processing. Despite over a century of research since its discovery, the Golgi architecture's intricate mechanisms still need to be fully understood. Here, we discuss that GMPs across different Eukaryotic lineages present a significant tendency to form biomolecular condensates. Moreover, we validated experimentally that members of the GRASP family also exhibit a strong tendency. Our findings offer a new perspective on the possible roles of protein disorder and condensation of GMPs in the Golgi organisation.

2024-07-01·Protein Science

The potential role of liquid–liquid phase separation in the cellular fate of the compartments for unconventional protein secretion

Article

作者: Costa-Filho, Antonio J ; da Silva, Marília D O ; Mendes, Luis Felipe S ; Rout, Saroj K ; Riek, Roland ; Gimenes, Carolina O

AbstractEukaryotic cells have developed intricate mechanisms for biomolecule transport, particularly in stressful conditions. This interdisciplinary study delves into unconventional protein secretion (UPS) pathways activated during starvation, facilitating the export of proteins bypassing most of the components of the classical secretory machinery. Specifically, we focus on the underexplored mechanisms of the GRASP's role in UPS, particularly in biogenesis and cargo recruitment for the vesicular‐like compartment for UPS. Our results show that liquid–liquid phase separation (LLPS) plays a key role in the coacervation of Grh1, the GRASP yeast homologue, under starvation‐like conditions. This association seems a precursor to the Compartment for Unconventional Protein Secretion (CUPS) biogenesis. Grh1's self‐association is regulated by electrostatic, hydrophobic, and hydrogen‐bonding interactions. Importantly, our study demonstrates that phase‐separated states of Grh1 can recruit UPS cargo under starvation‐like situations. Additionally, we explore how the coacervate liquid‐to‐solid transition could impact cells' ability to return to normal post‐stress states. Our findings offer insights into intracellular protein dynamics and cell adaptive responses to stress.

2024-05-01·Molecular Microbiology

GRASP negatively regulates the secretion of the virulence factor gp63 in Leishmania

Article

作者: Basak, Rituparna ; Mukhopadhyay, Amitabha ; Rai, Aakansha ; Kumar, Kamal

AbstractMetalloprotease‐gp63 is a virulence factor secreted by Leishmania. However, secretory pathway in Leishmania is not well defined. Here, we cloned and expressed the GRASP homolog from Leishmania. We found that Leishmania expresses one GRASP homolog of 58 kDa protein (LdGRASP) which localizes in LdRab1‐ and LPG2‐positive Golgi compartment in Leishmania. LdGRASP was found to bind with COPII complex, LdARF1, LdRab1 and LdRab11 indicating its role in ER and Golgi transport in Leishmania. To determine the function of LdGRASP, we generated LdGRASP knockout parasites using CRISPR‐Cas9. We found fragmentation of Golgi in Ld:GRASPKO parasites. Our results showed enhanced transport of non‐GPI‐anchored gp63 to the cell surface leading to higher secretion of this form of gp63 in Ld:GRASPKO parasites in comparison to Ld:WT cells. In contrast, we found that transport of GPI‐anchored gp63 to the cell surface is blocked in Ld:GRASPKO parasites and thereby inhibits its secretion. The overexpression of dominant‐negative mutant of LdRab1 or LdSar1 in Ld:GRASPKO parasites significantly blocked the secretion of non‐GPI‐anchored gp63. Interestingly, we found that survival of transgenic parasites overexpressing Ld:GRASP‐GFP is significantly compromised in macrophages in comparison to Ld:WT and Ld:GRASPKO parasites. These results demonstrated that LdGRASP differentially regulates Ldgp63 secretory pathway in Leishmania.