RESUMEN
Most cells tightly control the length of their cilia. The regulation likely involves intraflagellar transport (IFT), a bidirectional motility of multi-subunit particles organized into trains that deliver building blocks into the organelle. In Chlamydomonas, the anterograde IFT motor kinesin-2 consists of the motor subunits FLA8 and FLA10 and the nonmotor subunit KAP. KAP dissociates from IFT at the ciliary tip and diffuses back to the cell body. This observation led to the diffusion-as-a-ruler model of ciliary length control, which postulates that KAP is progressively sequestered into elongating cilia because its return to the cell body will require increasingly more time, limiting motor availability at the ciliary base, train assembly, building block supply, and ciliary growth. Here, we show that Chlamydomonas FLA8 also returns to the cell body by diffusion. However, more than 95% of KAP and FLA8 are present in the cell body and, at a given time, just ~1% of the motor participates in IFT. After repeated photobleaching of both cilia, IFT of fluorescent kinesin subunits continued indicating that kinesin-2 cycles from the large cell-body pool through the cilia and back. Furthermore, growing and full-length cilia contained similar amounts of kinesin-2 subunits and the size of the motor pool at the base changed only slightly with ciliary length. These observations are incompatible with the diffusion-as-a-ruler model, but rather support an "on-demand model," in which the cargo load of the trains is regulated to assemble cilia of the desired length.
RESUMEN
ABSTRACT: The association between progressive systemic sclerosis (PSS) and malignancy is uncommon. The possibility of development of small cell carcinoma lung (SCLC), among all the reported lung malignancies in PSS patients is lowest. A fifty-five year old non-smoker female diagnosed as PSS for 1 year presented to our outpatient department with dry cough for 2 months, shortness of breath for the last 1 month and progressive facial and right upper limb oedema for the last 15 days. Chest X-ray showed homogenous opacity in the right upper and mid zones of lung and the obliteration of both costophrenic angles. High resolution computed tomography (CT) of the thorax revealed a right upper lobe lung mass with bilateral minimal pleural effusion and the presence of bilateral reticular opacities, with basal predominance, associated with septal thickening, suggestive of interstitial lung disease of non-specific interstitial pneumonia pattern. CT guided fine needle aspiration cytology (FNAC) from the right upper lobe mass was suggestive of small cell carcinoma. Patient was improved after 6 cycles of chemotherapy with carboplatin and etoposide.