Ubiquitylation by Rab40b/Cul5 regulates Rap2 localization and activity during cell migration.

Cell migration is a complex process that involves coordinated changes in membrane transport and actin cytoskeleton dynamics. Ras-like small monomeric GTPases, such as Rap2, play a key role in regulating actin cytoskeleton dynamics and cell adhesions. However, how Rap2 function, localization, and activation are regulated during cell migration is not fully understood. We previously identified the small GTPase Rab40b as a regulator of breast cancer cell migration. Rab40b contains a suppressor of cytokine signaling (SOCS) box, which facilitates binding to Cullin5, a known E3 ubiquitin ligase component responsible for protein ubiquitylation. In this study, we show that the Rab40b/Cullin5 complex ubiquitylates Rap2. Importantly, we demonstrate that ubiquitylation regulates Rap2 activation as well as recycling of Rap2 from the endolysosomal compartment to the lamellipodia of migrating breast cancer cells. Based on these data, we propose that Rab40b/Cullin5 ubiquitylates and regulates Rap2-dependent actin dynamics at the leading edge, a process that is required for breast cancer cell migration and invasion.

Rab40-Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration.

Rab40b is a SOCS box-containing protein that regulates the secretion of MMPs to facilitate extracellular matrix remodeling during cell migration. Here, we show that Rab40b interacts with Cullin5 via the Rab40b SOCS domain. We demonstrate that loss of Rab40b-Cullin5 binding decreases cell motility and invasive potential and show that defective cell migration and invasion stem from alteration to the actin cytoskeleton, leading to decreased invadopodia formation, decreased actin dynamics at the leading edge, and an increase in stress fibers. We also show that these stress fibers anchor at less dynamic, more stable focal adhesions. Mechanistically, changes in the cytoskeleton and focal adhesion dynamics are mediated in part by EPLIN, which we demonstrate to be a binding partner of Rab40b and a target for Rab40b-Cullin5-dependent localized ubiquitylation and degradation. Thus, we propose a model where Rab40b-Cullin5-dependent ubiquitylation regulates EPLIN localization to promote cell migration and invasion by altering focal adhesion and cytoskeletal dynamics.

Successful medical drainage and surgical treatment for vertebral osteomyelitis and bilateral psoas abscess with gas formation caused by klebsiella pneumoniae in a diabetic patient.

OBJECTIVE: We describe the case of a diabetic patient who developed vertebral osteomyelitis and bilateral psoas abscess with gas formation due to klebsiella pneumoniae. METHODS: A 64-year-old woman with a 4-year history of type-2 diabetes mellitus was admitted to the Emergency Department. The subject had a 2-day history of high-grade fever associated with chills and a 5-hour history of consciousness. She received empirical treatment with febrifuge, after which her fever decreased. RESULTS: Her fever recurred after an interval of three hours. A computed tomography scan of the abdomen revealed vertebral osteomyelitis and bilateral psoas muscle abscess with gas formation. Blood culture and purulent fluid described the growth of the Klebsiella pneumoniae. The patient received antibiotic therapy and bilateral drainage therapy after the drainage catheter was placed into the abscess cavity by CT-guidance. Due to the serious damage to the vertebral column and permanent pain, the patient underwent minimally invasive internal spinal fixation and recovered successfully. CONCLUSION: A case of vertebral osteomyelitis and bilateral psoas abscess with gas formation caused by Klebsiella pneumoniae in a diabetic patient. Antibiotic therapy, drainage, and minimally invasive internal spinal fixation were performed, which enabled a good outcome.

Successful medical drainage and surgical treatment for vertebral osteomyelitis and bilateral psoas abscess with gas formation caused by klebsiella pneumoniae in a diabetic patient

SUMMARY OBJECTIVE: We describe the case of a diabetic patient who developed vertebral osteomyelitis and bilateral psoas abscess with gas formation due to klebsiella pneumoniae. METHODS: A 64-year-old woman with a 4-year history of type-2 diabetes mellitus was admitted to the Emergency Department. The subject had a 2-day history of high-grade fever associated with chills and a 5-hour history of consciousness. She received empirical treatment with febrifuge, after which her fever decreased. RESULTS: Her fever recurred after an interval of three hours. A computed tomography scan of the abdomen revealed vertebral osteomyelitis and bilateral psoas muscle abscess with gas formation. Blood culture and purulent fluid described the growth of the Klebsiella pneumoniae. The patient received antibiotic therapy and bilateral drainage therapy after the drainage catheter was placed into the abscess cavity by CT-guidance. Due to the serious damage to the vertebral column and permanent pain, the patient underwent minimally invasive internal spinal fixation and recovered successfully. CONCLUSION: A case of vertebral osteomyelitis and bilateral psoas abscess with gas formation caused by Klebsiella pneumoniae in a diabetic patient. Antibiotic therapy, drainage, and minimally invasive internal spinal fixation were performed, which enabled a good outcome.

RESUMO OBJETIVO: Descrever o caso de uma paciente diabética que desenvolveu osteomielite vertebral e abcesso bilateral do psoas com formação de gás causada por klebsiella pneumoniae. MÉTODOS: Uma mulher de 64 anos de idade, com 4 anos de histórico de diabetes mellitus tipo 2, foi admitida no Serviço de Emergência. A paciente apresentava um quadro de dias de febre alta acompanhada de calafrios e um histórico de 5 horas de consciência. Ela recebeu tratamento empírico com antitérmico, após o qual a febre diminuiu. RESULTADOS: A febre retornou após um intervalo de três horas. Uma tomografia computadorizada do abdome revelou osteomielite vertebral e abcesso bilateral do músculo psoas com formação de gás. A cultura do sangue e o fluido purulento revelaram o crescimento de Klebsiella pneumoniae. A paciente recebeu antibióticos e terapia de drenagem bilateral após o cateter de drenagem ser posicionado na cavidade do abscesso com auxílio de TC. Devido a sérios danos à coluna vertebral e a dor permanente, a paciente foi submetida à fixação vertebral interna minimamente invasiva e recuperou-se com sucesso. CONCLUSÃO: Um caso de osteomielite vertebral e abscesso do psoas bilateral com a formação de gás causada por Klebsiella pneumoniae em uma paciente diabética. Antibioticoterapia, drenagem e fixação vertebral interna minimamente invasiva foram realizadas, o que permitiu um bom resultado.