Target type: biologicalprocess
The directed movement of substances, in membrane-bounded vesicles, from the early sorting endosomes to the late sorting endosomes; transport occurs along microtubules and can be experimentally blocked with microtubule-depolymerizing drugs. [ISBN:0815316194, PMID:29980602]
Early endosome to late endosome transport is a crucial step in the endocytic pathway, responsible for delivering internalized cargo from the plasma membrane to the lysosomes for degradation or recycling. This process involves a series of intricate molecular events that ensure the efficient and selective sorting of various molecules.
The journey begins with the formation of early endosomes, small vesicles budding off from the plasma membrane. These endosomes are characterized by their relatively low pH (around 6.0-6.5) and a unique protein composition that includes Rab5, a small GTPase involved in early endosome formation and trafficking.
As the early endosomes mature, they acquire a more acidic internal environment, reaching a pH of approximately 5.5. This acidification is driven by the activity of vacuolar ATPases (V-ATPases) embedded in the endosomal membrane. The changing pH triggers a cascade of molecular events, including the recruitment of different proteins and the dissociation of others.
One of the key events during early endosome maturation is the recruitment of Rab7, another small GTPase, which is essential for late endosome formation and transport. Rab7 replaces Rab5 on the endosomal membrane, promoting the recruitment of other late endosomal proteins, such as the adaptor protein complex AP-3 and the tethering protein complex HOPS.
The transition from early to late endosomes also involves the fusion of multiple early endosomes into larger, more mature late endosomes. This fusion process is regulated by a complex interplay of proteins, including SNAREs, which mediate membrane fusion, and Rab GTPases, which orchestrate the recruitment of specific SNAREs to the endosomal membrane.
As late endosomes mature, they acquire a more densely packed appearance due to the accumulation of internalized cargo, including proteins, lipids, and even pathogens. These late endosomes are then transported to the lysosomes, where they fuse and deliver their cargo for final degradation. This final stage of the endocytic pathway ensures the efficient removal of unwanted cellular components, while also providing a mechanism for recycling valuable molecules back to the cell surface.'
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Protein | Definition | Taxonomy |
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Phosphatidylinositol 3-kinase catalytic subunit type 3 | A phosphatidylinositol 3-kinase catalytic subunit type 3 that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
Ras-related protein Rab-7a | A Ras-related protein Rab-7a that is encoded in the genome of human. [PRO:DNx, UniProtKB:P51149] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
2-[[benzamido(sulfanylidene)methyl]amino]-5,5-dimethyl-4,7-dihydrothieno[2,3-c]pyran-3-carboxylic acid | CID1067700: a pan-GTPase inhibitor; structure in first source | thienopyran | |
ML162 | ML162 : A monochlorobenzene that is benzene substituted by (chloroacetyl){2-oxo-2-[(2-phenylethyl)amino]-1-(thiophen-2-yl)ethyl}amino, chloro and methoxy groups at positions 1, 3 and 4, respectively. It is a covalent inhibitor of glutathione peroxidase 4 (GPX4) that induces ferroptosis in cells. | monochlorobenzenes; monomethoxybenzene; organochlorine compound; secondary carboxamide; tertiary carboxamide; thiophenes | EC 1.11.1.9 (glutathione peroxidase) inhibitor; ferroptosis inducer |
PI3-Kinase alpha Inhibitor 2 | organic heterobicyclic compound; organonitrogen heterocyclic compound; organosulfur heterocyclic compound | ||
idelalisib | idelalisib : A member of the class of quinazolines that is 5-fluoro-3-phenylquinazolin-4-one in which the hydrogen at position 2 is replaced by a (1S)-1-(3H-purin-6-ylamino)propyl group. used for for the treatment of refractory indolent non-Hodgkin's lymphoma and relapsed chronic lymphocytic leukemia. idelalisib: an antineoplastic agent and p110delta inhibitor; structure in first source | aromatic amine; organofluorine compound; purines; quinazolines; secondary amino compound | antineoplastic agent; apoptosis inducer; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor |
zstk474 | ZSTK-474 : A triamino-1,3,5-triazine that is 1,3,5-triazine in which two of the hydrogens have been replaced by morpholin-4-yl groups while the third hydrogen has been replaced by a 2-(difluoromethyl)benzimidazol-1-yl group. It is an inhibitor of phosphatidylinositol 3-kinase. | benzimidazoles; morpholines; organofluorine compound; triamino-1,3,5-triazine | antineoplastic agent; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor |
dactolisib | dactolisib : An imidazoquinoline that is 3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinoline substituted at position 1 by a 4-(1-cyanoisopropyl)phenyl group and at position 8 by a quinolin-3-yl group. A dual PI3K/mTOR inhibitor used in cancer treatment. dactolisib: antineoplastic agent that inhibits both phosphatidylinositol 3-kinase and mTOR | imidazoquinoline; nitrile; quinolines; ring assembly; ureas | antineoplastic agent; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor; mTOR inhibitor |
ku 60019 | |||
buparlisib | NVP-BKM120: a pan class I PI3 kinase inhibitor with antineoplastic activity; structure in first source | aminopyridine; aminopyrimidine; morpholines; organofluorine compound | antineoplastic agent; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor |
gdc 0941 | pictrelisib : A sulfonamide composed of indazole, morpholine, and methylsulfonyl-substituted piperazine rings bound to a thienopyrimidine ring. | indazoles; morpholines; piperazines; sulfonamide; thienopyrimidine | EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor |
gdc 0980 | |||
azd2014 | vistusertib: potent and selective dual mTORC1 and mTORC2 inhibitor; structure in first source | ||
pki 587 | gedatolisib: inhibits both phosphatidylinositol 3-kinase and mTOR; structure in first source | ||
5-(4-amino-1-propan-2-yl-3-pyrazolo[3,4-d]pyrimidinyl)-1,3-benzoxazol-2-amine | sapanisertib: an mTOR inhibitor | benzoxazole | |
ch 5132799 | CH 5132799: structure in first source | ||
torin 1 | torin 1 : A member of the class of pyridoquinolines that is 9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2-one bearing an additional 4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl substituent at position 1. It is a potent inhibitor of mTOR and exhibits anti-cancer properties. | N-acylpiperazine; N-arylpiperazine; organofluorine compound; pyridoquinoline; quinolines | antineoplastic agent; mTOR inhibitor |
gdc-0032 | |||
spautin-1 | |||
torin 2 | torin 2 : A member of the class of pyridoquinolines that is benzo[h][1,6]naphthyridin-2-one carrying additional 3-(trifluoromethyl)phenyl and 6-aminopyridin-3-yl substituents at positions 1 and 9 respectively. It is a potent inhibitor of mTOR and exhibits anti-cancer properties. | aminopyridine; organofluorine compound; primary amino compound; pyridoquinoline | antineoplastic agent; mTOR inhibitor |
cudc-907 | |||
sar245408 | |||
byl719 | proline derivative | ||
amg 511 | AMG 511: structure in first source | ||
cc-223 | |||
sar405 | SAR405: a Vps34 inhibitor with antineoplastic activity; structure in first source | ||
guanosine diphosphate | Guanosine Diphosphate: A guanine nucleotide containing two phosphate groups esterified to the sugar moiety. | guanosine 5'-phosphate; purine ribonucleoside 5'-diphosphate | Escherichia coli metabolite; mouse metabolite; uncoupling protein inhibitor |
guanosine triphosphate | Guanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety. | guanosine 5'-phosphate; purine ribonucleoside 5'-triphosphate | Escherichia coli metabolite; mouse metabolite; uncoupling protein inhibitor |