{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRab33B is a Golgi‐resident small GTPase that plays a central role in macroautophagy by directly interacting with autophagy proteins. In its GTP-bound state, Rab33B binds to Atg16L1 to recruit the ATG12–ATG5–ATG16L1 complex to nascent phagophores, a key step required for LC3 lipidation and proper autophagosome formation. These findings highlight how Rab33B modulates membrane remodeling events essential for cellular homeostasis, even under nutrient‐rich conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its autophagic function, Rab33B participates in non‐autophagic membrane trafficking at the Golgi. It associates with Ric1 and Rgp1, proteins that function as guanine nucleotide exchange factors for Rab6A, thereby forming a Rab cascade that is crucial for proper retrograde transport events within the Golgi network."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRab33B has also been implicated in viral replication processes. Investigations into hepatitis B virus (HBV) morphogenesis have shown that impairing Rab33B function—either through RNA interference or by expressing GDP-bound mutants—leads to defects in nucleocapsid formation and the membrane association of viral core proteins. This disruption in core protein trafficking and assembly ultimately results in diminished HBV propagation, underscoring a mechanistic link between autophagic pathways and viral particle assembly."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, unbiased RNA interference-based screening approaches have identified Rab33B as a critical factor in the intracellular trafficking of synthetic nanoparticles. This finding broadens the functional repertoire of Rab33B, suggesting its involvement in endocytic and cytoskeleton-associated pathways that govern the cellular uptake and precise intracellular transport of exogenous materials."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, clinical studies have revealed that pathogenic variants in the RAB33B gene are linked to rare skeletal dysplasias such as Smith–McCort Dysplasia. These observations suggest that aberrant Rab33B function—whether through impaired autophagosome formation or defective Golgi trafficking—can have severe developmental consequences, thus underscoring its importance beyond basic cell biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Takashi Itoh, Naonobu Fujita, Eiko Kanno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Golgi-resident small GTPase Rab33B interacts with Atg16L and modulates autophagosome formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e07-12-1231"}], "href": "https://doi.org/10.1091/mbc.e07-12-1231"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18448665"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18448665"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Niamh E Morgan, Meritxell B Cutrona, Jeremy C Simpson "}, {"type": "b", "children": [{"type": "t", "text": "Multitasking Rab Proteins in Autophagy and Membrane Trafficking: A Focus on Rab33b."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms20163916"}], "href": "https://doi.org/10.3390/ijms20163916"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31408960"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31408960"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Supansa Pantoom, Georgios Konstantinidis, Stephanie Voss, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RAB33B recruits the ATG16L1 complex to the phagophore via a noncanonical RAB binding protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2020.1822629"}], "href": "https://doi.org/10.1080/15548627.2020.1822629"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32960676"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32960676"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mintu Chandra, Runjhun Saran, Sunando Datta "}, {"type": "b", "children": [{"type": "t", "text": "Deciphering the role of Atg5 in nucleotide dependent interaction of Rab33B with the dimeric complex, Atg5-Atg16L1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2016.03.043"}], "href": "https://doi.org/10.1016/j.bbrc.2016.03.043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26975471"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26975471"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ganesh V Pusapati, Giovanni Luchetti, Suzanne R Pfeffer "}, {"type": "b", "children": [{"type": "t", "text": "Ric1-Rgp1 complex is a guanine nucleotide exchange factor for the late Golgi Rab6A GTPase and an effector of the medial Golgi Rab33B GTPase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.414565"}], "href": "https://doi.org/10.1074/jbc.M112.414565"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23091056"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23091056"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Tatjana Döring, Reinhild Prange "}, {"type": "b", "children": [{"type": "t", "text": "Rab33B and its autophagic Atg5/12/16L1 effector assist in hepatitis B virus naked capsid formation and release."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Microbiol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cmi.12398"}], "href": "https://doi.org/10.1111/cmi.12398"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25439980"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25439980"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Smrithi Salian, Tae-Joon Cho, Shubha R Phadke, et al. 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