Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mammalian cells, including neurons, use macroautophagy (here 'autophagy') to degrade damaged proteins and organelles, and recycle nutrients in response to starvation and other forms of cell stress. The basic cellular machinery responsible for autophagy is highly conserved from yeast to mammals. However, evidence for specific adaptations to more complex organisms and in highly differentiated cells (e. g. neurons) remains limited. RILP (Rab interacting lysosomal protein) mediates retrograde transport of late endosomes (LEs) in nonneuronal mammalian cells. We have now found that RILP plays additional important, fundamental roles in neuronal autophagosome (AP) transport, and, more surprisingly, in AP biogenesis, and cargo turnover as well. RILP accomplishes these tasks via sequential interactions with key autophagosomal components - ATG5 and LC3 - as well as the microtubule motor protein cytoplasmic dynein (Figure 1A). We found further that RILP expression and behavior are controlled by MTOR kinase, linking RILP to a potentially wide range of physiological and pathophysiological functions.
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PMID:A RILP-regulated pathway coordinating autophagosome biogenesis with transport. 3259 6

Primary cilia are sensors of chemical and mechanical signals in the extracellular environment. The formation of primary cilia (i.e. ciliogenesis) requires dynamic membrane trafficking events, and several Rab small GTPases, key regulators of membrane trafficking, have recently been reported to participate in ciliogenesis. However, the precise mechanisms of Rab-mediated membrane trafficking during ciliogenesis remain largely unknown. In the present study, we used a collection of siRNAs against 62 human Rabs to perform a comprehensive knockdown screening for Rabs that regulate serum starvation-induced ciliogenesis in human telomerase reverse transcriptase retinal pigment epithelium 1 (hTERT-RPE1) cells and succeeded in identifying Rab34 as an essential Rab. Knockout (KO) of Rab34, but not of Rabs previously reported to regulate ciliogenesis (e.g. Rab8 and Rab10) in hTERT-RPE1 cells, drastically impaired serum starvation-induced ciliogenesis. Rab34 was also required for serum starvation-induced ciliogenesis in NIH/3T3 cells and MCF10A cells but not for ciliogenesis in Madin-Darby canine kidney (MDCK)-II cysts. We then attempted to identify a specific region(s) of Rab34 that is essential for ciliogenesis by performing deletion and mutation analyses of Rab34. Unexpectedly, instead of a specific sequence in the switch II region, which is generally important for recognizing effector proteins (e.g. Rab interacting lysosomal protein [RILP]), a unique long N-terminal region of Rab34 before the conserved GTPase domain was found to be essential. These findings suggest that Rab34 is an atypical Rab that regulates serum starvation-induced ciliogenesis through its unique N-terminal region.
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PMID:A comprehensive analysis of Rab GTPases reveals a role for Rab34 in serum starvation-induced primary ciliogenesis. 3266 61